DONA ORA
Pubblicazioni recenti - cardiac fibrosis
-
Stratified Treatment of Heart Failure with preserved Ejection Fraction: rationale and design of the STADIA-HFpEF trial.
ESC Heart Fail2020 Oct;():. doi: 10.1002/ehf2.13055.
Scheffer Mariëlle, Driessen-Waaijer Annet, Hamdani Nazha, Landzaat Jochem W D, Jonkman Nini H, Paulus Walter J, van Heerebeek Loek,
Abstract
AIMS:
High myocardial stiffness in heart failure with preserved ejection fraction (HFpEF) is attributed to comorbidity-induced structural and functional remodelling through inflammation and oxidative stress affecting coronary microvascular endothelial cells and cardiomyocytes, which augments interstitial fibrosis and cardiomyocyte stiffness. In murine and human HFpEF myocardium, sodium glucose co-transporter 2 (SGLT2) inhibition ameliorates cardiac microvascular endothelial cell and cardiomyocyte oxidative stress, while enhancing myocardial protein kinase G activity and lowering titin-based cardiomyocyte stiffness. Failure of previous HFpEF outcome trials refocuses attention to improving pathophysiological insight and trial design with better phenotyping of patients and matching of therapeutic targets to prevailing pathogenetic mechanisms. SGLT2 inhibition could represent a viable therapeutic option especially in HFpEF patients in whom high diastolic left ventricular (LV) stiffness is predominantly caused by elevated cardiomyocyte stiffness and associated endothelial dysfunction, whereas HFpEF patients with extensive myocardial fibrosis might be less responsive. This study aims to investigate a stratified treatment approach, using dapagliflozin in heart failure patients with preserved ejection fraction without evidence of significant myocardial fibrosis.
METHODS AND RESULTS:
The Stratified Treatment to Ameliorate DIAstolic left ventricular stiffness in early Heart Failure with preserved Ejection Fraction (STADIA-HFpEF) is a Phase II, randomized, 2 × 2 crossover trial, evaluating the efficacy of 13 weeks of treatment with dapagliflozin 10 mg od in 26 patients with HFpEF, with normal cardiac magnetic resonance imaging-derived extracellular volume. The co-primary endpoint is echocardiographically derived change in E/e'/LV end-diastolic volume index and change in mean LV e'.
CONCLUSIONS:
The STADIA-HFpEF trial will be the first study to evaluate the direct effects of dapagliflozin on amelioration of LV stiffness, using histological phenotyping to discern early HFpEF.
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
Guarda su PubMed
-
Clofibrate improves myocardial ischemia-induced damage through regulation of renin-angiotensin system and favours a pro-vasodilator profile in left ventricle.
J Pharmacol Sci2020 Dec;144(4):218-228. doi: S1347-8613(20)30095-5.
Ibarra-Lara L, Sánchez-Aguilar M, Del Valle-Mondragón L, Soria-Castro E, Cervantes-Pérez L G, Pastelín-Hernández G, Sánchez-Mendoza A,
Abstract
Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPAR? activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.
Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Guarda su PubMed
-
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.
Guarda su PubMed
-
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.
Guarda su PubMed
-
Cardiac sarcoidosis: diagnosis and management.
Rev Cardiovasc Med2020 Sep;21(3):321-338. doi: 10.31083/j.rcm.2020.03.102.
Markatis Eleftherios, Afthinos Andreas, Antonakis Emmanouil, Papanikolaou Ilias C,
Abstract
Sarcoidosis is a chronic inflammatory disease of unknown etiology characterized by multi-organ involvement. End-organ disease consists of granulomatous inflammation, which if left untreated or not resolved spontaneously, leads to permanent fibrosis and end-organ dysfunction. Cardiac involvement and fibrosis in sarcoidosis occur in 5-10% of cases and is becoming increasingly diagnosed. This is due to increased clinical awareness among clinicians and new diagnostic modalities, since magnetic resonance imaging and positron-emission tomography are emerging as "gold standard" tools replacing endomyocardial biopsy. Despite this progress, isolated cardiac sarcoidosis is difficult to differentiate from other causes of arrhythmogenic cardiomyopathy. Cardiac fibrosis leads to congestive heart failure, arrhythmias and sudden cardiac death. Immunosuppressives (mostly corticosteroids) are used for the treatment of cardiac sarcoidosis. Implantable devices like a cardioverter-defibrillator may be warranted in order to prevent sudden cardiac death. In this article current trends in the pathophysiology, diagnosis and management of cardiac sarcoidosis will be reviewed focusing on published research and latest guidelines. Lastly, a management algorithm is proposed.
© 2020 Markatis et al. Published by IMR press.
Guarda su PubMed
-
Pulse Oximetry Values in Newborns with Critical Congenital Heart Disease upon ICU Admission at Altitude.
Int J Neonatal Screen2018 Dec;4(4):30. doi: 10.3390/ijns4040030.
Kim John S, Ariefdjohan Merlin W, Sontag Marci K, Rausch Christopher M,
Abstract
Pulse oximetry screening for critical congenital heart disease (CCHD) has been recommended by the American Academy of Pediatrics (AAP). The objectives of this study are to describe saturation data, and to evaluate the effectiveness of AAP-recommended pulse oximetry screening guidelines applied retrospectively to a cohort of newborns with known CCHD at moderate altitude (5557 feet, Aurora, Colorado). Data related to seven critical congenital heart disease diagnoses were extracted from electronic health records (pulse oximetry, prostaglandin administration, and oxygen supplementation). Descriptive epidemiologic data were calculated. 158 subjects were included in this analysis; the AAP pulse oximetry screening protocol was applied to 149 subjects. Mean pre-ductal and post-ductal pulse oximetry values of the infants known to have CCHD at 24 h of life were 87.1% ± 7.2 and 87.8% ± 6.3, respectively. Infants treated with prostaglandins and oxygen had lower oximetry readings. The screening algorithm would have identified 80.5% of infants with known CCHDs (120/149 subjects). Additionally, sequential pulse oximetry screening based on the AAP-recommended protocol was able to identify a true positive screen capture rate of 80.5% at moderate altitude.
© 2018 by the authors.
Guarda su PubMed
-
Haplo-insufficiency of Tmem43 in cardiac myocytes activates the DNA damage response pathway leading to a Late-Onset Senescence-Associated pro-fibrotic cardiomyopathy.
Cardiovasc Res2020 Oct;():. doi: cvaa300.
Rouhi Leila, Cheedipudi Sirisha M, Chen Suet Nee, Fan Siyang, Lombardi Raffaella, Chen Xiaofan, Coarfa Cristian, Robertson Matthew J, Gurha Priyatansh, Marian Ali J,
Abstract
AIMS:
Arrhythmogenic cardiomyopathy (ACM) encompasses a genetically heterogeneous group of myocardial diseases whose manifestations are sudden cardiac death, cardiac arrhythmias, heart failure, and in a subset fibro-adipogenic infiltration of the myocardium. Mutations in the TMEM43 gene, encoding transmembrane protein 43 (TMEM43) are known to cause ACM. The purpose of the study was to gain insights into the molecular pathogenesis of ACM caused by TMEM43 haploinsufficiency.
METHODS AND RESULTS:
The Tmem43 gene was specifically deleted in cardiac myocytes by crossing the Myh6-Cre and floxed Tmem43 mice. Myh6-Cre: Tmem43W/F mice showed an age-dependent phenotype characterized by an increased mortality, cardiac dilatation and dysfunction, myocardial fibrosis, adipogenesis, and apoptosis. Sequencing of cardiac myocyte transcripts prior to and after the onset of cardiac phenotype predicted early activation of the TP53 pathway. Increased TP53 activity was associated with increased levels of markers of DNA damage response (DDR), and a subset of senescence-associated secretary phenotype (SASP). Activation of DDR, TP53, SASP and their selected downstream effectors, including phospho-SMAD2 and phospho-SMAD3 were validated by alternative methods, including immunoblotting. Expression of SASP was associated with epithelial-mesenchymal transition (EMT) and age-dependent expression of myocardial fibrosis and apoptosis in the Myh6-Cre: Tmem43W/F mice.
CONCLUSIONS:
TMEM43 haplo-insufficiency is associated with activation of the DDR and the TP53 pathways, which lead to increased expression of SASP and an age-dependent expression of a pro-fibrotic cardiomyopathy. Given that TMEM43 is a nuclear envelope protein and our previous data showing deficiency of another nuclear envelope protein, namely lamin A/C, activates the DDR/TP53 pathway, we surmise that DNA damage is a shared mechanism in the pathogenesis of cardiomyopathies caused by mutations involving nuclear envelope proteins.
TRANSLATIONAL PERSPECTIVE:
The data indicate that the DNA damage response (DDR) to double stranded DNA breaks (DSBs) is activated in a mouse model of cardiomyopathy caused by haplo-insufficiency of the Tmem43 gene. The TMEM43 gene is a known cause of arrhythmogenic cardiomyopathy in humans. The DDR activates the TP53 pathway and leads to expression of senescence associated secretary phenotype (SASP), such as TGF?1, which induce a senescence-associated pro-fibrotic cardiomyopathy.These findings along with our previous data identify the DDR as a putative common mechanism in the pathogenesis of cardiomyopathies, and likely in the pathogenesis of over two dozen diseases, caused by mutations in the nuclear envelope proteins (envelopathies).
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
Guarda su PubMed
-
Carcinoid Heart Disease: Pathophysiology, Pathology, Clinical Manifestations, and Management.
Cardiology2020 Oct;():1-9. doi: 10.1159/000507847.
Jin Chengyue, Sharma Ajay Nair, Thevakumar Balasingam, Majid Muhammad, Al Chalaby Shahad, Takahashi Nene, Tanious Ashraf, Arockiam Aro Daniela, Beri Neil, Amsterdam Ezra A,
Abstract
Carcinoid heart disease (CHD) is a rare and potentially lethal manifestation of an advanced carcinoid (neuroendocrine) tumor. The pathophysiology of CHD is related to vasoactive substances secreted by the tumor, of which serotonin is most prominent in the pathophysiology of CHD. Serotonin stimulates fibroblast growth and fibrogenesis, which can lead to cardiac valvular fibrosis. CHD primarily affects right heart valves, causing tricuspid and pulmonic regurgitation and less frequently stenosis of these valves. Left heart valves are usually spared because vasoactive substances such as serotonin are enzymatically inactivated in the lung vasculature. The pathology of CHD is characterized by plaque-like deposition of fibrous tissue on valvular cusps, leaflets, papillary muscles, chordae, and ventricular walls. Symptomatic CHD usually presents between 50 and 70 years of age, initially as dyspnea and fatigue. Echocardiography is the mainstay of imaging and demonstrates thickened right heart valves with limited mobility and regurgitation. Treatment focuses on control of the underlying carcinoid syndrome, targeting subsequent valvular heart disease and managing consequent heart failure. Surgical valve replacement and catheter-directed valve procedures may be effective for selected patients with CHD.
© 2020 S. Karger AG, Basel.
Guarda su PubMed
-
The role of stem cells in treating coronary artery disease in 2018.
Indian J Thorac Cardiovasc Surg2018 Dec;34(Suppl 3):340-348. doi: 10.1007/s12055-018-0739-7.
Michler Robert E,
Abstract
The last decade has witnessed the publication of a number of stem cell clinical trials, primarily using bone marrow-derived cells as the injected cell. Much has been learned through these "first-generation" clinical trials. The advances in our understanding include the following: (1) cell therapy is safe; (2) cell therapy has been mildly effective; and (3) human bone marrow-derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels. The primary mechanism of action for cell therapy is now believed to be through paracrine effects that include the release of cytokines, chemokines, and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate endogenous regenerative mechanisms through endogenous circulating or site-specific stem cells. The current direction for clinical trials includes the use of stem cells capable of cardiac lineage.
© Indian Association of Cardiovascular-Thoracic Surgeons 2018.
Guarda su PubMed
-
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.
Guarda su PubMed
-
The feasibility and diagnostic value of intravoxel incoherent motion diffusion-weighted imaging in the assessment of myocardial fibrosis in hypertrophic cardiomyopathy patients.
Eur J Radiol2020 Oct;132():109333. doi: S0720-048X(20)30522-2.
Wu Rui, An Dong-Aolei, Shi Ruo-Yang, Chen Bing-Hua, Wu Chong-Wen, Jiang Meng, Xu Jian-Rong, Wu Lian-Ming, Pu Jun,
Abstract
PURPOSE:
To investigate the feasibility and diagnostic value of intravoxel incoherent motion (IVIM) in the assessment of myocardial fibrosis in hypertrophic cardiomyopathy (HCM) patients.
METHODS:
Fifty-five HCM patients underwent IVIM diffusion-weighted cardiovascular resonance imaging; Cine, T1 mapping, IVIM and late gadolinium enhancement (LGE) were performed. The relationship of strain, pre T1, extracellular volume (ECV), IVIM-derived parameters (D, D* and f) and LGE were analyzed based on 16 American Heart Association segments. Abnormal segments of myocardial fibrosis were defined as: the presence of LGE (LGE+) or ECV???29.6 %.
RESULTS:
D parameter was significantly increased in LGE?+?vs LGE- (1.89?±?0.14 ?m/ms vs. 1.63?±?0.12 ?m/ms, p?
CONCLUSIONS:
IVIM DW-CMR has proven to be ingenious in the investigation of myocardial fibrosis; D* and f parameters may have potential value to assess the perfusion status of fibrotic regions in HCM patients.
Copyright © 2020 Elsevier B.V. All rights reserved.
Guarda su PubMed
-
Mechanical extraction of cardiac implantable electronic devices leads with long dwell time: Efficacy and safety of the step up approach.
Pacing Clin Electrophysiol2020 Oct;():. doi: 10.1111/pace.14094.
Lensvelt Leontine M H, Egorova Anastasia D, Schalij Martin J, Yilmaz Dilek, Kennergren Charles, Bootsma Marianne, van Erven Lieselot,
Abstract
The aim of this study was to evaluate the efficacy and safety of the stepwise mechanical transvenous lead extraction approach in a patient population with chronically implanted transvenous leads with a long dwell time. From January 2014 till December 2018, all lead extractions with lead dwell time ? 5 years performed at our tertiary centre were retrospectively analysed. A total of 173 leads, from 78 patients (median age 68 years; 81% male) with a median dwell time of 9 years (IQR 5) were extracted, with 3 or more leads in 42% of the patients. Right atrial leads: 41%, right ventricular pacing leads: 16%, ICD leads: 31% (72% dual coil); coronary sinus leads: 12%. The majority (75%) of the leads had an active fixation. Most frequent indication for extraction was pocket infection/erosion (76%). Overall clinical success was 97% and complete procedural success was 93%. Venous patency, assessed with venous angiography, was well preserved in 93% of the cases. The overall procedural complication rate was 3,8% (2.6% major and 1,3% minor). Despite the complexity of the population and a very long dwell time (median 9 years), a clinical success rate of 97% was achieved with the stepwise mechanical approach. Analysis of impeding progression of pectoral extraction suggests that dense fibrosis and sharp lead curvature in the transvenous trajectory pose a challenge. Complication rate was low and acute venous patency was generally well preserved. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Left ventricular remodeling and dysfunction in primary aldosteronism.
J Hum Hypertens2020 Oct;():. doi: 10.1038/s41371-020-00426-y.
Tsai Cheng-Hsuan, Pan Chien-Ting, Chang Yi-Yao, Chen Zheng-Wei, Wu Vin-Cent, Hung Chi-Sheng, Lin Yen-Hung,
Abstract
Primary aldosteronism (PA) is a common cause of secondary hypertension and is associated with worse cardiovascular outcomes. The elevated aldosterone in PA leads to left ventricular (LV) remodeling and dysfunction. In recent decades, clinical studies have demonstrated worse LV remodeling including increased LV mass and cardiac fibrosis in patients with PA compared to patients with essential hypertension. Several mechanisms may explain the process of aldosterone-induced LV remodeling, including directly profibrotic and hypertrophic effects of aldosterone on myocardium, increased reactive oxygen species and profibrotic molecules, dysregulation of extracellular matrix metabolism, endothelium dysfunction and circulatory macrophages activation. LV remodeling causes LV diastolic and systolic dysfunction, which may consequently lead to clinical complications such as heart failure, atrial fibrillation, ischemic heart disease, and other vascular events. Adequate treatment with adrenalectomy or medical therapy can improve LV remodeling and dysfunction in PA patients. In this review, we discuss the mechanisms of aldosterone-induced LV remodeling and provide an up-to-date review of clinical research about LV remodeling-related heart structural changes, cardiac dysfunction, and their clinical impacts on patients with PA.
Guarda su PubMed
-
A high-stringency blueprint of the human proteome.
Nat Commun2020 Oct;11(1):5301. doi: 10.1038/s41467-020-19045-9.
Adhikari Subash, Nice Edouard C, Deutsch Eric W, Lane Lydie, Omenn Gilbert S, Pennington Stephen R, Paik Young-Ki, Overall Christopher M, Corrales Fernando J, Cristea Ileana M, Van Eyk Jennifer E, Uhlén Mathias, Lindskog Cecilia, Chan Daniel W, Bairoch Amos, Waddington James C, Justice Joshua L, LaBaer Joshua, Rodriguez Henry, He Fuchu, Kostrzewa Markus, Ping Peipei, Gundry Rebekah L, Stewart Peter, Srivastava Sanjeeva, Srivastava Sudhir, Nogueira Fabio C S, Domont Gilberto B, Vandenbrouck Yves, Lam Maggie P Y, Wennersten Sara, Vizcaino Juan Antonio, Wilkins Marc, Schwenk Jochen M, Lundberg Emma, Bandeira Nuno, Marko-Varga Gyorgy, Weintraub Susan T, Pineau Charles, Kusebauch Ulrike, Moritz Robert L, Ahn Seong Beom, Palmblad Magnus, Snyder Michael P, Aebersold Ruedi, Baker Mark S,
Abstract
The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
Guarda su PubMed
-
[Diagnosing cardiac amyloidosis in magnetic resonance imaging: The discriminating factors].
Ann Cardiol Angeiol (Paris)2020 Oct;():. doi: S0003-3928(20)30132-3.
Goïorani 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.
Guarda su PubMed
-
Methods for histological characterization of cryo-induced myocardial infarction in a rat model.
Acta Histochem2020 Oct;122(7):151624. doi: S0065-1281(20)30123-9.
Alonzo Matthew, Delgado Monica, Cleetus Carol, Kumar Shweta Anil, Thakur Vikram, Chattopadhyay Munmun, Joddar Binata,
Abstract
Ligation of the left anterior descending (LAD) coronary artery has been commonly employed to induce myocardial infarction (MI) in animals; however, it is known to pose setbacks in the form of cardiac arrhythmias and unpredictable areas of necrotic damage. Cryo-infarction is an alternate method that has been adopted to create a reproducible model of a myocardial injury. In this study, Sprague-Dawley rats were subjected to thoracotomy followed by cryo-induced infarction of the heart, while the control-sham group was only subjected to thoracotomy following which the heart was collected from all animals. Tissue sections were stained with hematoxylin and eosin and analyzed to determine cardiac muscle density, fiber length, and fiber curvature. Observations revealed reduced muscle density, cardiac fiber length, and distorted fibers in infarcted tissue sections. Gomori's Trichrome staining was performed on tissue sections to study the effects of post MI on collagen, which showed enhanced intensity of collagen staining indicating fibrosis for the experimental models as compared to the sham models, an established consequence to myocardial injury. Immunohistochemical staining of the tissue sections with DAPI and connexin-43 (Cx-43) revealed that there was reduced DAPI staining and a less pronounced expression of Cx-43 in the experimental samples as compared to the sham samples. Results implied significant cell damage resulting from the cryo-infarction, subsequently disrupting and disaggregating the functional Cx-43 junction in cardiac myocytes, which is essential for normal and healthy cardiac physiology and function. This quantitative histological study of cryo-induced MI in a rat model can aid others attempting to optimize MI models in rats via cryo-injury, to study cardiac disease progression, and to aid in the construction of engineered cardiac tissues.
Copyright © 2020 Elsevier GmbH. All rights reserved.
Guarda su PubMed
-
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.
Guarda su PubMed
-
Opioid-Induced Immunomodulation: Consequences for the Experimental Coxsackievirus B3-Induced Myocarditis Model.
Biology (Basel)2020 Oct;9(10):. doi: E335.
Pappritz Kathleen, Linthout Sophie Van,
Abstract
Myocarditis is an inflammatory disorder of the heart predominantly caused by infectious agents. Since more than sixty years, the Coxsackievirus B3 (CVB3)-induced myocarditis mouse model is the experimental model used to investigate viral myocarditis. The pathogenesis of viral myocarditis is conceptually a multiphase process, initiated by the infection of cardiomyocytes, followed by activation of the immune system, and resulting in myocardial fibrosis and left ventricular dysfunction. In parallel to the direct infection of the heart, CVB3 replicates in lymphatic organs such as the pancreas. Due to infection of the pancreas, the model of experimental CVB3-induced myocarditis is estimated as a severe burden for the challenged animals. Application of analgesics in frame of the animal welfare act (European directive 2010/63/EU) is more and more becoming a matter of debate. For this purpose, we summarized published studies for 13 different opioids and discussed their potential impact on CVB3-induced myocarditis. In addition, with this summary we also want to provide guidance for researchers beyond the myocarditis field to estimate the impact of opioids on the immune system for their specific model. In the literature, both immunosuppressive as well as immune-activating effects of opioids have been described, but examinations in experimental CVB3-induced myocarditis have still not been reported so far. Based on the existing publications, administration of opioids in experimental CVB3-induced myocarditis might result in more severe disease progression, including higher mortality, or a less pronounced myocarditis model, failing to be used for the establishment of new treatment options. Taken together, the applicability of opioids in experimental CVB3-induced myocarditis and in inflammatory models in general needs to be carefully evaluated and further investigated.
Guarda su PubMed
-
Rectification of cavernosal fibrosis and veno-occlusive dysfunction by administration of suberoylanilide hydroxamic acid in a rat model of cavernosal nerve injury: Comparison with a PDE5 inhibitor.
Andrology2020 Oct;():. doi: 10.1111/andr.12922.
Cho Min Chul, Lee Junghoon, Son Hwancheol, Kim Soo Woong,
Abstract
BACKGROUND:
Cavernosal fibrosis, which is induced by cavernosal nerve (CN) injury and progresses with time, is the main cause of cavernosal veno-occlusive dysfunction (CVOD) after radical prostatectomy.
OBJECTIVES:
To determine if daily oral administration of suberoylanilide-hydroxamic-acid (SAHA; vorinostat) for 5-weeks from the immediate post-injury period after CN injury would rectify CVOD by suppressing cavernosal fibrosis and normalizing HDAC pathway in a rat model of CN-crush-injury (CNCI), and to compare the results with those obtained using chronic administration of PDE5-inhibitors (a positive control).
METHODS:
Fifty-six 12-week-old rats were randomized into the four groups: sham-surgery (S), CNCI (I), CNCI treated with daily administration of 25.0 mg/kg SAHA (V) or 20.0 mg/kg udenafil (P). Group-V and Group-P received the respective treatment for 5-weeks from the following day after CNCI. At 5-weeks after surgery, dynamic-infusion-cavernosometry (DIC), histological-staining, and Western-blot analysis were performed.
RESULTS:
Group-I had a significantly decreased papaverine-response, higher maintenance-rate or drop-rate, lower smooth muscle (SM)/collagen ratio, decreased SM content, and increased protein expression of HDAC2, HDAC3, TGF-?1, and collagen-1, compared with Group-S. The three DIC parameters in Group-V and Group-P significantly improved compared to those in Group-I. Except for the maintenance-rate, the improvement in papaverine-response and drop-rate in Group-V was not significantly different from that in Group-P. Group-V and Group-P showed the rectification of SM/collagen ratio and protein expression of TGF-?1 or collagen-1. SM content was improved in Group-P, but not in Group-V. Group-V showed the normalization of protein expression of both HDAC2 and HDAC3, whereas protein expression of only HDAC2 was partially restored in Group-P.
DISCUSSION:
Treatment strategies targeting the HDAC pathway might be helpful to alleviate CVOD induced by CN injury.
CONCLUSIONS:
According to our data, chronic administration of SAHA improves post-injury CVOD by suppressing cavernosal fibrosis via rectifying the HDAC/TGF-?1 pathway in nerve-injured rats, comparable to that with PDE5-inhibitors.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
MMP9 inhibition increases autophagic flux in chronic heart failure.
Am J Physiol Heart Circ Physiol2020 Oct;():. doi: 10.1152/ajpheart.00032.2020.
Nandi Shyam Sundar, Katsurada Kenichi, Sharma Neeru M, Anderson Daniel R, Mahata Sushil K, Patel Kaushik P,
Abstract
An increased matrix metalloprotease9 (MMP9) during post-myocardial infarction (post-MI) exacerbates ischemia-induced chronic heart failure (CHF). Autophagy is cardioprotective during CHF, however, whether increased MMP9 suppressed autophagic activity in CHF is unknown. This study aimed to determine whether the increased MMP9 suppressed autophagic flux, and MMP9 inhibition increased autophagic flux in the heart of rats with Post-MI CHF. Sprague-Dawley rats underwent either Sham or coronary artery ligation, 6-8 weeks prior to being treated with MMP9-inhibitor for 7days, followed by cardiac autophagic flux measurement using lysosomal inhibitor BafilomycinA1. Further, autophagic flux was measured in vitro by treating H9c2 cardiomyocytes with two independent pharmacological MMP9 inhibitors, Salvianolic-Acid-B (SalB) or MMP9-inhibitor-I, and CRISPR/cas9-mediated MMP9 genetic ablation. CHF rats showed cardiac infarct, significantly increased left ventricular end-diastolic pressure (LVEDP), and increased MMP9 activity and fibrosis in the peri-infarct areas of left-ventricular myocardium. The autophagic markers LC3B-II and p62 measurement with lysosomal inhibition showed decreased autophagic flux in the peri-infarct myocardium. Treatment with SalB for 7days in CHF rats decreased MMP9 activity, cardiac fibrosis, and increased autophagic flux in the peri-infarct myocardium. As an in vitro corollary study, measurement of autophagic flux in H9c2 cardiomyocytes and fibroblasts showed that pharmacological inhibition or genetic ablation of MMP9 upregulates autophagic flux. These data are consistent with our observations that MMP9 inhibition upregulates autophagic flux in the heart of rats with CHF. In conclusion, the results in this study suggest that the beneficial outcome of MMP9 inhibition on pathological cardiac remodeling is in part mediated by improved autophagic flux.
Guarda su PubMed
