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Pubblicazioni recenti - cardiac hypertrophy
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The chromogranin A fragment reveals how a single change in the protein sequence exerts strong cardioregulatory effects by engaging neuropilin-1.
Acta Physiol (Oxf)2020 Oct;():e13570. doi: 10.1111/apha.13570.
Rocca Carmine, Grande Fedora, Granieri Maria Concetta, Colombo Barbara, De Bartolo Anna, Giordano Francesca, Rago Vittoria, Amodio Nicola, Tota Bruno, Cerra Maria Carmela, Rizzuti Bruno, Corti Angelo, Angelone Tommaso, Pasqua Teresa,
Abstract
AIM:
Chromogranin A (CgA), a 439-residue long protein, is an important cardiovascular regulator and a precursor of various bio-active fragments. Under stressful/pathological conditions, CgA cleavage generates the CgA proangiogenic fragment. The present work investigated the possibility that human CgA influences the mammalian cardiac performance, evaluating the role of its C-terminal sequence.
METHODS:
Hemodynamic assessment was performed on an ex vivo Langendorff rat heart model, while mechanistic studies were performed using perfused hearts, H9c2 cardiomyocytes, and in silico.
RESULTS:
On the ex vivo heart CgA elicited direct dose-dependent negative inotropism and vasodilation, while CgA , a fragment lacking the C-terminal R residue, was ineffective. Antibodies against the PGPQLR C-terminal sequence abrogated the CgA -dependent cardiac and coronary modulation. Ex vivo studies showed that CgA -dependent effects were mediated by endothelium, neuropilin-1 (NRP1) receptor, Akt/NO/Erk1,2 pathways, nitric oxide (NO) production and S-nitrosylation. In vitro experiments on H9c2 cardiomyocytes indicated that CgA also induced eNOS activation directly on the cardiomyocyte component by NRP1 targeting and NO involvement and provided beneficial action against isoproterenol-induced hypertrophy, by reducing the increase of cell surface area and brain natriuretic peptide (BNP) release. Molecular docking and all-atom molecular dynamics simulations strongly supported the hypothesis that the C-terminal R residue of CgA directly interacts with NRP1.
CONCLUSION:
These results suggest that CgA is a new cardioregulatory hormone and that the removal of R represents a critical switch for turning "off" its cardioregulatory activity.
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DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism.
Heart Vessels2020 Oct;():. doi: 10.1007/s00380-020-01711-z.
Furukawa Nozomi, Koitabashi Norimichi, Matsui Hiroki, Sunaga Hiroaki, Umbarawan Yogi, Syamsunarno Mas Rizky A A, Yamaguchi Aiko, Obokata Masaru, Hanaoka Hirofumi, Yokoyama Tomoyuki, Kurabayashi Masahiko,
Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used incretin-based therapy for the treatment of type 2 diabetes. We investigated the cardioprotective effect of a DPP-4 inhibitor, vildagliptin (vilda), on myocardial metabolism and cardiac performance under pressure overload. Mice were treated with either vehicle or vilda, followed by transverse aortic constriction (TAC). After 3 weeks of TAC, cardiac hypertrophy and impairment of systolic function were attenuated in vilda-treated mice. Pressure-volume analysis showed that vilda treatment significantly improved left-ventricular contractile efficiency in TAC heart. Myocardial energy substrate analysis showed that vilda treatment significantly increased glucose uptake as well as fatty acid uptake. Fibroblast growth factor 21 (FGF21), a peptide involved in the regulation of energy metabolism, increased in TAC heart and was further increased by vilda treatment. FGF21 was strongly expressed in cardiac fibroblasts than in cardiomyocytes in mouse heart after TAC with vilda treatment. Vilda treatment markedly induced FGF21 expression in human cardiac fibroblasts through a sirtuin (Sirt) 1-mediated pathway, suggesting that fibroblast-mediated FGF21 expression may regulate energy metabolism and exert vilda-mediated beneficial effects in stressed heart. Vilda induced a metabolic regulator, FGF21 expression in cardiac fibroblasts via Sirt1, and increased contractile efficiency in murine pressure-overloaded heart.
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Renal sympathetic denervation attenuates left ventricle hypertrophy in spontaneously hypertensive rats by suppressing the Raf/MEK/ERK signaling pathway.
Clin Exp Hypertens2020 Oct;():1-9. doi: 10.1080/10641963.2020.1833022.
Xiao Bing, Liu Fan, Jin Ye-Hui, Jin Ya-Qiong, Wang Li, Lu Jing-Chao, Yang Xiu-Chun,
Abstract
OBJECTIVE:
To explore the effect of renal sympathetic denervation (RSD) on left ventricle hypertrophy and the Raf/MEK/ERK signaling pathway in spontaneously hypertensive rats (SHRs).
METHODS:
SHRs were divided into SHR, SHR + Sham, SHR + RSD and SHR + U0126 groups, with WKY rats as the baseline controls. The blood pressure of rats was observed, while myocardial fibrosis was evaluated through Masson staining. Thereafter, real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to determine the levels of myocardial-hypertrophy-related markers, and Western blotting was used to measure the activity of the Raf/MEK/ERK signaling pathway.
RESULTS:
In comparison with the WKY group, significant increases were observed in the systolic pressure and diastolic pressure of rats from the other four groups at different time points after surgery. In addition, rats in these groups had obvious increases in LVMI, renal NE and IVSd and decreases in LVEDd, LVEF and LVFS. In addition, the CVF of myocardial tissues was increased, with the upregulation of ANP, BNP and ?-MHC and the downregulation of ?-MHC. For the activity of the Raf/MEK/ERK signaling pathway, the levels of -Raf/Raf, -MEK/MEK and -ERK1/2/ERK1/2 were all remarkably elevated (all .05). Further comparison with the SHR group showed that the above indexes in the rats were significantly improved in the RSD group and SHR + U0126 group (all .05).
CONCLUSION:
RSD may decrease blood pressure, mitigate hypertension-induced left ventricle hypertrophy and improve cardiac function efficiently in SHRs via the suppression of the Raf/MEK/ERK signaling pathway.
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Innate Immune Nod1/RIP2 Signaling is Essential for Cardiac Hypertrophy, but Requires Mitochondrial Antiviral Signaling Protein (MAVS) for Signal Transductions and Energy Balance.
Circulation2020 Oct;():. doi: 10.1161/CIRCULATIONAHA.119.041213.
Lin Han-Bin, Naito Kotaro, Oh Yena, Farber Gedaliah, Kanaan Georges, Valaperti Alan, Dawood Fayez, Zhang Liyong, Li Guo Hua, Smyth David, Moon Mark, Liu Youan, Liang Wenbin, Rotstein Benjamin, Philpott Dana, Kim Kyoung-Han, Harper Mary-Ellen, Liu Peter P,
Abstract
Cardiac hypertrophy is a key biological response to injurious stresses such as pressure overload and when excessive can lead to heart failure. Innate immune activation by danger signals, through intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain-containing protein 1(Nod1) and its adaptor receptor-interacting protein 2 (RIP2), might play a major role in cardiac remodeling and progression to heart failure. We hypothesize that Nod1/RIP2 are major contributors to cardiac hypertrophy, but may not be sufficient to fully express the phenotype alone. To elucidate the contribution of Nod1/RIP2 signaling to cardiac hypertrophy, we randomized Nod1, RIP2 or wild-type (WT) mice to transverse aortic constriction (TAC) or sham operations. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. Nod1 and RIP2 proteins were up-regulated in the heart after TAC, and this was paralleled by increased expression of mitochondrial proteins, including mitochondrial antiviral signaling protein (MAVS). Nod1 and RIP2 mice subjected to TAC exhibited better survival, improved cardiac function and decreased cardiac hypertrophy. Downstream signal transduction pathways that regulate inflammation and fibrosis including NF-?B and MAPK-GATA4/p300, were reduced in both Nod1 and RIP2 mice after TAC compared with WT mice. Co-immunoprecipitation of extracted cardiac proteins and confocal immunofluorescence microscopy showed that Nod1/ RIP2 interaction was robust and that this complex also included MAVS as an essential component. Suppression of MAVS expression attenuated the complex formation, NF-?B signalling and myocyte hypertrophy. Interrogation of mitochondrial function compared in the presence or ablation of MAVS revealed that MAVS serves to suppress mitochondrial energy output and mediate fission/fusion related dynamic changes. The latter is possibly linked to mitophagy during cardiomyocytes stress, which may provide an intriguing link between innate immune activation and mitochondrial energy balance under stress or injury conditions. We have identified that innate immune Nod1/RIP2 signaling is a major contributor to cardiac remodeling following stress. This process is critically joined by and regulated through the mitochondrial danger signal adapter MAVS. This novel complex coordinates remodeling, inflammatory response and mitochondrial energy metabolism in stressed cardiomyocytes. Thus Nod1/RIP2/MAVS signaling complex may represent an attractive new therapeutic approach toward heart failure.
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Prospective Assessment of Subclinical Cardiovascular Damage and Associated Factors in Liver Transplant Recipients.
Transpl Int2020 Oct;():. doi: 10.1111/tri.13773.
Memaran Nima, Küpper Claire, Borchert-Mörlins Bianca, von Wick Anika, Bauer Elena, Jäckel Elmar, Maasoumy Benjamin, Vondran Florian Wolfgang Rudolf, Sugianto Rizky Indrameikha, von der Born Jeannine, Schmidt Bernhard Magnus Wilhelm, Melk Anette,
Abstract
Cardiovascular (CV) disease plays a major role after liver transplantation (LT). This prospective study assessed subclinical CV damage after LT by measuring pulse-wave velocity (PWV), intima-media thickness (IMT) and left-ventricular mass index (LVMI) and characterized associated risk factors. We included 112 patients with a median 1.8 years after LT (q1-q3 0.9-9.2). 53% (n=59) of patients had ?2 annual assessments (median follow-up 1.6 years, q1-q3 1.1-2.0), with a total of 195 assessments. We found increased PWV (indicating arteriosclerosis) in 16% (n=17), elevated IMT in 5% (n=5; indicating atherosclerosis) and increased LVMI in 25% (n=24; indicating left-ventricular hypertrophy). A linear mixed model analysis using all 195 assessments revealed that higher age and systolic blood pressure (BP) were associated with higher PWV (?=0.069, p<0.001 and ?=0.022, p=0.005) and higher IMT (?=0.005, p<0.001 and ?=0.001, p=0.029), while higher body-mass index was associated with higher IMT (?=0.004, p=0.023). Higher systolic BP (?=0.200, p=0.034), male sex (?=8.847, p=0.031) and lower glomerular filtration rate (?=-0,288, p<0.001) were associated with higher LVMI. Our data highlights not only the rate of subclinical CV damage in LT patients, but also the impact of classical CV risk factors (such as BP and body-mass index) which outweighed LT-related factors. These modifiable risk factors are suitable targets for interventions to reduce CV morbidity in LT patients.
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Dietary Carbohydrates Restriction Inhibits The Development Of Cardiac Hypertrophy And Heart Failure.
Cardiovasc Res2020 Oct;():. doi: cvaa298.
Nakamura Michinari, Odanovic Natalija, Nakada Yasuki, Dohi Satomi, Zhai Peiyong, Ivessa Andreas, Yang Zhi, Abdellatif Maha, Sadoshima Junichi,
Abstract
AIMS:
A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how a LC diet impacts on cardiac pathology during hemodynamic stress remains elusive. This study evaluated the effects of a LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodeling.
METHODS AND RESULTS:
Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4?weeks, echocardiographic, hemodynamic, histological and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3?, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3? cardiac-specific knockout mice. ?-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signaling.
CONCLUSIONS:
Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.
TRANSLATIONAL PERSPECTIVE:
Hemodynamic stress, such as hypertension, induces pathological cardiac hypertrophy, leading to heart failure. There is growing evidence that modulating components of diet affects cardiac function in humans, although the causality and underlying mechanisms are poorly understood. Our study demonstrates that strict restriction of dietary carbohydrates supplemented with either fat or proteins during acute hemodynamic stress attenuates the development and progression of cardiac hypertrophy and heart failure by activating distinct anti-hypertrophic and cardioprotective signaling mechanisms. The study suggests that it would be useful to investigate the therapeutic benefit of carbohydrate restriction in patients with hypertension and cardiac hypertrophy in clinical studies.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
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Isoproterenol-induced hypertrophy of neonatal cardiac myocytes and H9c2 cell is dependent on TRPC3-regulated Ca1.2 expression.
Cell Calcium2020 Oct;92():102305. doi: S0143-4160(20)30147-0.
Han Jung Woo, Kang Choeun, Kim Yonjung, Lee Min Goo, Kim Joo Young,
Abstract
Ca1.2 and transient receptor potential canonical channel 3 (TRPC3) are two proteins known to have important roles in pathological cardiac hypertrophy; however, such roles still remain unclear. A better understanding of these roles is important for furthering the clinical understanding of heart failure. We previously reported that Trpc3-knockout (KO) mice are resistant to pathologic hypertrophy and that their Ca1.2 protein expression is reduced. In this study, we aimed to examine the relationship between these two proteins and characterize their role in neonatal cardiomyocytes. We measured Ca1.2 expression in the hearts of wild-type (WT) and Trpc3 mice, and examined the effects of Trpc3 knockdown and overexpression in the rat cell line H9c2. We also compared the hypertrophic responses of neonatal cardiomyocytes cultured from Trpc3 mice to a representative hypertrophy-causing drug, isoproterenol (ISO), and measured the activity of nuclear factor of activated T cells 3 (NFAT3) in neonatal cardiomyocytes (NCMCs). We inhibited the L-type current with nifedipine, and measured the intracellular calcium concentration using Fura-2 with 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced Ba influx. When using the Trpc3-mediated Ca influx, both intracellular calcium concentration and calcium influx were reduced in Trpc3-KO myocytes. Not only was the expression of Ca1.2 greatly reduced in Trpc3-KO cardiac lysate, but the size of the Ca1.2 currents in NCMCs was also greatly reduced. When NCMCs were treated with Trpc3 siRNA, it was confirmed that the expression of Ca1.2 and the intracellular nuclear transfer activity of NFAT decreased. In H9c2 cells, the ISO activated- and verapamil inhibited- Ca influxes were dramatically attenuated by Trpc3 siRNA treatment. In addition, it was confirmed that both the expression of Ca1.2 and the size of H9c2 cells were regulated according to the expression and activation level of TRPC3. We found that after stimulation with ISO, cell hypertrophy occurred in WT myocytes, while the increase in size of Trpc3-KO myocytes was greatly reduced. These results suggest that not only the cell hypertrophy process in neonatal cardiac myocytes and H9c2 cells were regulated according to the expression level of Ca1.2, but also that the expression level of Ca1.2 was regulated by TRPC3 through the activation of NFAT.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Si-Miao-Yong-An decoction preserves cardiac function and regulates GLC/AMPK/NF-?B and GLC/PPAR?/PGC-1? pathways in diabetic mice.
Biomed Pharmacother2020 Oct;132():110817. doi: S0753-3322(20)31010-6.
Li Lin, Chen Xiangyang, Su Congping, Wang Qing, Li Rui, Jiao Wenchao, Luo Hui, Tian Yimiao, Tang Jiayang, Li Xiaoxuan, Liu Bin, Wang Wei, Zhang Dongwei, Guo Shuzhen,
Abstract
BACKGROUND:
Diabetic cardiomyopathy (DCM) is a main cause of heart failure and death in diabetic patients. However, countermeasures to limit the development of this disease remain insufficient. Si-Miao-Yong-An decoction (SMYA), a Chinese herbal prescription, exhibits both lipid-lowering and cardiovascular preserving effects, and may have an effect on DCM management.
PURPOSE:
The current study is aimed to investigate the effects of SMYA on the cardiac function in diabetic mice and the underlying mechanisms involved.
METHODS:
Streptozotocin-induced diabetic mice were fed intragastrically with SMYA every day for 15 weeks. Cardiac function was assessed by echocardiograph. Histopathological alterations in the heart were determined by hematoxylin/eosin, wheat germ agglutinin, Masson's trichrome, Terminal dUTP nick end-labeling, Oil red O staining, and transmission electron microscopy. The potential involvements of GLC/AMPK/NF-?B and GLC/PPAR?/PGC-1? signaling pathways were investigated by western blot and/or immunohistochemical staining.
RESULTS:
Treatment of diabetic mice with SMYA improved insulin sensitivity, and attenuated the increases of water consumption, food intake, blood glucose, and serum GLC. Furthermore, SMYA ameliorated cardiac systolic and diastolic functions, suppressed the myocardial hypertrophy, fibrosis, apoptosis, inflammation, and lipid accumulation as well as preserved the myofilaments arrangement and mitochondrial integrity. Finally, SMYA downregulated the expressions of GCGR, PGC-1?, PPAR? and the phosphorylation of NF-?B, as well as upregulated the phosphorylation of AMPK in the hearts of diabetic mice.
CONCLUSIONS:
SMYA may ameliorate glucolipid metabolism and cardiac function through the regulation of GLC/AMPK/NF-?B and GLC/PPAR?/PGC-1? signaling pathways in diabetic mice, suggesting that this prescription could provide a new source of drug candidates to protect against DCM.
Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
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Oxygenation-Sensitive Cardiovascular Magnetic Resonance in Hypertensive Heart Disease With Left Ventricular Myocardial Hypertrophy and Non-Left Ventricular Myocardial Hypertrophy: Insight From Altered Mechanics and Cardiac BOLD Imaging.
J Magn Reson Imaging2020 Oct;():e27401. doi: 10.1002/jmri.27401.
Chen Bing-Hua, Wu Rui, An Dong-Aolei, Shi Ruo-Yang, Yao Qiu-Ying, Lu Qing, Hu Jiani, Jiang Meng, Deen James, Chandra Ankush, Xu Jian-Rong, Wu Lian-Ming,
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Differential diagnosis of apical hypertrophic cardiomyopathy and apical displacement of the papillary muscles: a multimodality imaging point of view.
Echocardiography2020 Oct;():. doi: 10.1111/echo.14895.
Ünlü Serkan, Özden Tok Özge, Avc? Demir Fulya, Papadopoulos Konstantinos, Monaghan Mark J,
Abstract
Apical hypertrophic cardiomyopathy (ApHCM) and apical displacement of papillary muscles (ADPM) are two different pathologies with a number of similar imaging findings that may hamper adequate diagnosis. While ApHCM is associated with increased rate of mortality, ADPM commonly presents with a benign course and differential diagnosis is of great importance. Clinical assessment and 2D echocardiography cannot sufficiently differentiate these conditions, however, and advanced echocardiographic methods may facilitate diagnosis. Although echocardiography is the first-line imaging method in the diagnostic algorithm, cardiac magnetic resonance imaging (CMRI) is the gold standard for evaluating patients due to good spatial resolution and myocardial tissue characterization abilities. When CMRI is contraindicated, cardiac computed tomography may be an alternative reliable method that can also give information about the coronary anatomy. Nuclear imaging may also provide supplementary data regarding hypertrophy and coronary arteries when there is a suspicion of ischemia.
© 2020 Wiley Periodicals LLC.
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Effect of Regional Upper Septal Hypertrophy on Echocardiographic Assessment of Left Ventricular Mass and Remodeling in Aortic Stenosis.
J Am Soc Echocardiogr2020 Oct;():. doi: S0894-7317(20)30591-5.
Guzzetti Ezequiel, Tastet Lionel, Annabi Mohamed-Salah, Capoulade Romain, Shen Mylčne, Bernard Jérémy, García Julio, Le Ven Florent, Arsenault Marie, Bédard Elisabeth, Larose Eric, Clavel Marie-Annick, Pibarot Philippe,
Abstract
BACKGROUND:
Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR).
METHODS:
One hundred six patients (mean age, 63 ± 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ? 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis.
RESULTS:
The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 ± 31 g; BSB, +59 ± 32 g; ML, +54 ± 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10 ± 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB).
CONCLUSIONS:
Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.
Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
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Effect of Irisin on Pressure Overload-Induced Cardiac Remodeling.
Arch Med Res2020 Oct;():. doi: S0188-4409(20)30081-3.
Peng Qing, Ding Ruilin, Wang Xiaojie, Yang Ping, Jiang Feng, Chen Xiaoping,
Abstract
BACKGROUND:
Irisin has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in cardiac remodeling.
AIM OF THE STUDY:
This study aimed to determine the potential role of irisin in cardiac remodeling and explore potential mechanisms.
METHODS:
A total of 40 rats that underwent transverse abdominal aortic constriction (TAC) surgery or sham operation were divided into four groups: sham + saline (NS), sham + irisin, TAC + NS, and TAC + irisin. After 6 weeks of treatment, echocardiography was performed to assess in vivo cardiac morphology. The left ventricular myocardium was prepared and observed by pathological examination. The effect of irisin on cardiomyocyte apoptosis and the expression of oxidative stress and cardiac hypertrophy markers were observed. Then, the effect of irisin on the Akt signaling system was also detected.
RESULTS:
The rats in the TAC group displayed obvious signs of cardiac dysfunction and cardiac hypertrophy, and irisin treatment could reverse these changes. Irisin could inhibit the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 and xanthine oxidase in TAC rats and increase the expression of antioxidant enzymes. Furthermore, the expression of phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylated glycogen synthase kinase 3? (p-GSK3?) was much higher in the cardiac remodeling groups (p <0.05 vs. sham rats). Irisin could relieve the inhibition effect and reduce the expression level of these three proteins.
CONCLUSIONS:
Irisin treatment could significantly improve cardiac remodeling by inhibiting oxidative stress via attenuating the Akt signaling activation.
Copyright © 2020. Published by Elsevier Inc.
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[Diagnosing cardiac amyloidosis in magnetic resonance imaging: The discriminating factors].
Ann Cardiol Angeiol (Paris)2020 Oct;():. doi: S0003-3928(20)30132-3.
Goďorani F, Dagrenat C, Brocchi J, Couppie P, Leddet P,
Abstract
Infiltrative cardiomyopathies refers to deposits of substances in the myocardial tissue resulting in a structural abnormality and/or alteration of cardiac function. Cardiac amyloidosis is an extracellular infiltration of amyloid fibril. Cardiac magnetic resonance imaging (MRI) is essential (in the) for its diagnosis. MRI sequences (morphological, viability and parametric mapping) allow a structural and dynamic analysis of the cardiac function as well as a characterization of the myocardial tissue: edema, fatty infiltration, fibrosis. In cardiac amyloidosis, the morphological sequences classically highlight ventricular hypertrophy and thickening of the heart valves. Ventricular functions are assessed by the cine sequences (The cine sequences make it possible to evaluate the ventricular functions.) The viability sequences show (a more diffuse distribution of hypersignals) an abnormal pattern of late gadolinium enhancement in both circumferential and sub-endocardial distribution. The relaxometry sequences or parametric T1 and/or T2 mapping allow the spatial visualization of quantitative changes of the myocardium. The presence of macroscopic myocardial edema or fibrosis causes a prolongation of the native T1 and an increase of the extracellular volume.
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
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MicroRNAs as Biomarkers of Systemic Changes in Response to Endurance Exercise-A Comprehensive Review.
Diagnostics (Basel)2020 Oct;10(10):. doi: E813.
Soplinska Aleksandra, Zareba Lukasz, Wicik Zofia, Eyileten Ceren, Jakubik Daniel, Siller-Matula Jolanta M, De Rosa Salvatore, Malek Lukasz A, Postula Marek,
Abstract
Endurance sports have an unarguably beneficial influence on cardiovascular health and general fitness. Regular physical activity is considered one of the most powerful tools in the prevention of cardiovascular disease. MicroRNAs are small particles that regulate the post-transcription gene expression. Previous studies have shown that miRNAs might be promising biomarkers of the systemic changes in response to exercise, before they can be detected by standard imaging or laboratory methods. In this review, we focused on four important physiological processes involved in adaptive changes to various endurance exercises (namely, cardiac hypertrophy, cardiac myocyte damage, fibrosis, and inflammation). Moreover, we discussed miRNAs' correlation with cardiopulmonary fitness parameter (VO). After a detailed literature search, we found that miR-1, miR-133, miR-21, and miR-155 are crucial in adaptive response to exercise.
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Left ventricular dysfunction and reversible pulmonary hypertension secondary to severe pneumonia in a background of sepsis: a case report and review of the literature.
Ann Palliat Med2020 Sep;9(5):3629-3642. doi: 10.21037/apm-20-1198.
Gitonga Elaine N, Wang Junwu, Yu Shengwei, Wu Na, Shen Haitao,
Abstract
Pneumonia is a well-recognized respiratory infection associated with substantial morbidity and mortality. Despite its effects on the respiratory system, pneumonia can cause or exacerbate cardiovascular complications through various mechanisms. The two main mechanisms that are described in this case report are hypoxia-induced pulmonary hypertension and the effect of sepsis on the cardiovascular system. Pulmonary hypertension (PH) is a disease characterized by raised pulmonary arterial pressure due to a progressive increase in pulmonary vascular resistance, inevitably leading to right ventricular (RV) afterload. For our case, the situation was complicated by sepsis, which further worsened the myocardial function causing left ventricular hypertrophy and left ventricular dysfunction. The main goal of this case report is to highlight the fact that cardiovascular events due to pneumonia are a potential complication even in young patients who are without any comorbidities. We present a case of a 14-year-old patient who presented with symptoms of cough, hemoptysis, fever, chest pain, and dyspnea. After the necessary investigations, he was diagnosed with severe pneumonia, sepsis, moderate PH, and left ventricular dysfunction. The treatment course was focused on stabilizing the patient by oxygen supplementation, treating the underlying cause with the use of antibiotics, and decreasing the already raised arterial pressures through vasodilator therapy. After the patient went through the proper course of treatment, there was a marked improvement in his general condition.Cardiac complications due to pneumonia are potential complications even in relatively young patients who have no noted comorbidities. Clinicians should be aware of these potentially fatal complications of pneumonia and appreciate the significance of this association for timely recognition, diagnosis, and management of these complications.
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Inhibition of Interleukin-6 Signaling Attenuates Aortitis, Left Ventricular Hypertrophy and Arthritis in Interleukin-1 Receptor Antagonist Deficient Mice.
Clin Sci (Lond)2020 Oct;():. doi: CS20201036.
Hada Yoshiko, Uchida Haruhito A, Mukai Tomoyuki, Kojima Fumiaki, Yoshida Masashi, Takeuchi Hidemi, Kakio Yuki, Otaka Nozomu, Morita Yoshitaka, Wada Jun,
Abstract
The aim of this study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into 4 groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight % of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis.
Copyright 2020 The Author(s).
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Zinc Finger Protein ZBTB20 protects against cardiac remodelling post-myocardial infarction via ROS-TNF?/ASK1/JNK pathway regulation.
J Cell Mol Med2020 Oct;():. doi: 10.1111/jcmm.15961.
Li Fangfang, Yang Yiming, Xue Chuanyou, Tan Mengtong, Xu Lu, Gao Jianbo, Xu Luhong, Zong Jing, Qian Wenhao,
Abstract
This study aims to determine the efficacy of Zinc finger protein ZBTB20 in treatment of post-infarction cardiac remodelling. For this purpose, left anterior descending (LAD) ligation was operated on mice to induce myocardial infarction (MI) with sham control group as contrast and adeno-associated virus (AAV9) system was used to deliver ZBTB20 to mouse heart by myocardial injection with vehicle-injected control group as contrast two weeks before MI surgery. Then four weeks after MI, vehicle-treated mice with left ventricular (LV) remodelling underwent deterioration of cardiac function, with symptoms of hypertrophy, interstitial fibrosis, inflammation and apoptosis. The vehicle-injected mice also showed increase of infarct size and decrease of survival rate. Meanwhile, the ZBTB20-overexpressed mice displayed improvement after MI. Moreover, the anti-apoptosis effect of ZBTB20 was further confirmed in H9c2 cells subjected to hypoxia in vitro. Further study suggested that ZBTB20 exerts cardioprotection by inhibiting tumour necrosis factor ?/apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase 1/2 (JNK1/2) signalling, which was confirmed by shRNA-JNK adenoviruses transfection or a JNK activator in vitro as well as ASK1 overexpression in vivo. In summary, our data suggest that ZBTB20 could alleviate cardiac remodelling post-MI. Thus, administration of ZBTB20 can be considered as a promising treatment strategy for heart failure post-MI. Significance Statement: ZBTB20 could alleviate cardiac remodelling post-MI via inhibition of ASK1/JNK1/2 signalling.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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Cardiovascular toxicity of PI3K? inhibitors.
Clin Sci (Lond)2020 Oct;134(19):2595-2622. doi: 10.1042/CS20200302.
Sadasivan Chandu, Zhabyeyev Pavel, Labib Dina, White James A, Paterson D Ian, Oudit Gavin Y,
Abstract
The phosphoinositide 3-kinases (PI3Ks) are a family of intracellular lipid kinases that phosphorylate the 3'-hydroxyl group of inositol membrane lipids, resulting in the production of phosphatidylinositol 3,4,5-trisphosphate from phosphatidylinositol 4,5-bisphosphate. This results in downstream effects, including cell growth, proliferation, and migration. The heart expresses three PI3K class I enzyme isoforms (?, ?, and ?), and these enzymes play a role in cardiac cellular survival, myocardial hypertrophy, myocardial contractility, excitation, and mechanotransduction. The PI3K pathway is associated with various disease processes but is particularly important to human cancers since many gain-of-function mutations in this pathway occur in various cancers. Despite the development, testing, and regulatory approval of PI3K inhibitors in recent years, there are still significant challenges when creating and utilizing these drugs, including concerns of adverse effects on the heart. There is a growing body of evidence from preclinical studies revealing that PI3Ks play a crucial cardioprotective role, and thus inhibition of this pathway could lead to cardiac dysfunction, electrical remodeling, vascular damage, and ultimately, cardiovascular disease. This review will focus on PI3K?, including the mechanisms underlying the adverse cardiovascular effects resulting from PI3K? inhibition and the potential clinical implications of treating patients with these drugs, such as increased arrhythmia burden, biventricular cardiac dysfunction, and impaired recovery from cardiotoxicity. Recommendations for future directions for preclinical and clinical work are made, highlighting the possible role of PI3K? inhibition in the progression of cancer-related cachexia and female sex and pre-existing comorbidities as independent risk factors for cardiac abnormalities after cancer treatment.
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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Cardiac magnetic resonance T2 mapping and feature tracking in athlete's heart and HCM.
Eur Radiol2020 Oct;():. doi: 10.1007/s00330-020-07289-4.
Gastl Mareike, Lachmann Vera, Christidi Aikaterini, Janzarik Nico, Veulemans Verena, Haberkorn Sebastian, Holzbach Leonie, Jacoby Christoph, Schnackenburg Bernhard, Berrisch-Rahmel Susanne, Zeus Tobias, Kelm Malte, Bönner Florian,
Abstract
OBJECTIVES:
Distinguishing hypertrophic cardiomyopathy (HCM) from left ventricular hypertrophy (LVH) due to systematic training (athlete's heart, AH) from morphologic assessment remains challenging. The purpose of this study was to examine the role of T2 mapping and deformation imaging obtained by cardiovascular magnetic resonance (CMR) to discriminate AH from HCM with (HOCM) or without outflow tract obstruction (HNCM).
METHODS:
Thirty-three patients with HOCM, 9 with HNCM, 13 strength-trained athletes as well as individual age- and gender-matched controls received CMR. For T2 mapping, GRASE-derived multi-echo images were obtained and analyzed using dedicated software. Besides T2 mapping analyses, left ventricular (LV) dimensional and functional parameters were obtained including LV mass per body surface area (LVMi), interventricular septum thickness (IVS), and global longitudinal strain (GLS).
RESULTS:
While LVMi was not significantly different, IVS was thickened in HOCM patients compared to athlete's. Absolute values of GLS were significantly increased in patients with HOCM/HNCM compared to AH. Median T2 values were elevated compared to controls except in athlete's heart. ROC analysis revealed T2 values (AUC 0.78) and GLS (AUC 0.91) as good parameters to discriminate AH from overall HNCM/HOCM.
CONCLUSION:
Discrimination of pathologic from non-pathologic LVH has implications for risk assessment of competitive sports in athletes. Multiparametric CMR with parametric T2 mapping and deformation imaging may add information to distinguish AH from LVH due to HCM.
KEY POINTS:
? Structural analyses using T2 mapping cardiovascular magnetic resonance imaging (CMR) may help to further distinguish myocardial diseases. ? To differentiate pathologic from non-pathologic left ventricular hypertrophy, CMR including T2 mapping was obtained in patients with hypertrophic obstructive/non-obstructive cardiomyopathy (HOCM/HNCM) as well as in strength-trained athletes. ? Elevated median T2 values in HOCM/HNCM compared with athlete's may add information to distinguish athlete's heart from pathologic left ventricular hypertrophy.
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Bakuchiol Alleviates Hyperglycemia-Induced Diabetic Cardiomyopathy by Reducing Myocardial Oxidative Stress via Activating the SIRT1/Nrf2 Signaling Pathway.
Oxid Med Cell Longev2020 ;2020():3732718. doi: 10.1155/2020/3732718.
Ma Wenshuai, Guo Wangang, Shang Fujun, Li Yan, Li Wei, Liu Jing, Ma Chao, Teng Jiwei,
Abstract
Bakuchiol (BAK), a monoterpene phenol reported to have exerted a variety of pharmacological effects, has been related to multiple diseases, including myocardial ischemia reperfusion injury, pressure overload-induced cardiac hypertrophy, diabetes, liver fibrosis, and cancer. However, the effects of BAK on hyperglycemia-caused diabetic cardiomyopathy and its underlying mechanisms remain unclear. In this study, streptozotocin-induced mouse model and high-glucose-treated cell model were conducted to investigate the protective roles of BAK on diabetic cardiomyopathy, in either the presence or absence of SIRT1-specific inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA. Our data demonstrated for the first time that BAK could significantly abate diabetic cardiomyopathy by alleviating the cardiac dysfunction, ameliorating the myocardial fibrosis, mitigating the cardiac hypertrophy, and reducing the cardiomyocyte apoptosis. Furthermore, BAK achieved its antifibrotic and antihypertrophic actions by inhibiting the TGF-1/Smad3 pathway, as well as decreasing the expressions of fibrosis- and hypertrophy-related markers. Intriguingly, these above effects of BAK were largely attributed to the remarkable activation of SIRT1/Nrf2 signaling, which eventually strengthened cardiac antioxidative capacity by elevating the antioxidant production and reducing the reactive oxygen species generation. However, all the beneficial results were markedly abolished with the administration of EX527, SIRT1 siRNA, or Nrf2 siRNA. In summary, these novel findings indicate that BAK exhibits its therapeutic properties against hyperglycemia-caused diabetic cardiomyopathy by attenuating myocardial oxidative damage via activating the SIRT1/Nrf2 signaling.
Copyright © 2020 Wenshuai Ma et al.
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