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Pubblicazioni recenti - cardiac hypertrophy
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miR-145 transgenic mice develop cardiopulmonary complications leading to postnatal death.
Physiol Rep2021 Sep;9(17):e15013. doi: 10.14814/phy2.15013.
Thomas Shelby, Manivannan Sathiyanarayanan, Sawant Dwitiya, Kodigepalli Karthik M, Garg Vidu, Conway Simon J, Lilly Brenda,
Abstract
BACKGROUND:
Both downregulation and elevation of microRNA miR-145 has been linked to an array of cardiopulmonary phenotypes, and a host of studies suggest that it is an important contributor in governing the differentiation of cardiac and vascular smooth muscle cell types.
METHODS AND RESULTS:
To better understand the role of elevated miR-145 in utero within the cardiopulmonary system, we utilized a transgene to overexpress miR-145 embryonically in mice and examined the consequences of this lineage-restricted enhanced expression. Overexpression of miR-145 has detrimental effects that manifest after birth as overexpressor mice are unable to survive beyond postnatal day 18. The miR-145 expressing mice exhibit respiratory distress and fail to thrive. Gross analysis revealed an enlarged right ventricle, and pulmonary dysplasia with vascular hypertrophy. Single cell sequencing of RNA derived from lungs of control and miR-145 transgenic mice demonstrated that miR-145 overexpression had global effects on the lung with an increase in immune cells and evidence of leukocyte extravasation associated with vascular inflammation.
CONCLUSIONS:
These data provide novel findings that demonstrate a pathological role for miR-145 in the cardiopulmonary system that extends beyond its normal function in governing smooth muscle differentiation.
© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
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Naringin attenuates high glucose-induced injuries and inflammation by modulating the leptin-JAK2/STAT3 pathway in H9c2 cardiac cells.
Arch Med Sci2021 ;17(5):1145-1157. doi: 10.5114/aoms.2019.84854.
Luo Changjun, Ke Xiao, Xiong Si, Sun Yun, Xu Qing, Zhang Wei, Lei Yiyan, Ding Yiqian, Zhen Yulan, Feng Jianqiang, Cheng Fei, Chen Jingfu,
Abstract
Introduction:
Our previous study showed that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting p38 mitogen-activated protein kinase (MAPK). Leptin induces hypertrophy in rat cardiomyocytes via p38/MAPK activation. The present study aimed to test the hypothesis that leptin-Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), which are responsible for leptin's functions, are involved in HG-induced injuries and cardioprotective effects of NRG in cardiomyocytes.
Material and methods:
H9c2 cells were exposed to HG for 24 h to establish a cardiomyocyte injury model. Cells were pretreated with NRG and other drugs before exposure to HG. Protein expression was measured by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Apoptotic cells were assessed by Hoechst 33258 staining assay. Intracellular reactive oxygen species levels were determined by dichlorofluorescein diacetate staining. Mitochondrial membrane potential was evaluated using JC-1. An enzyme-linked immunosorbent assay was performed to determine the inflammatory cytokines.
Results:
NRG significantly attenuated HG-induced increases in leptin and Ob-R expression. Pretreatment with either a leptin antagonist (LA) or NRG markedly ameliorated HG-induced elevation of phosphorylated (p)-JAK2 and p-STAT3, respectively. Pretreatment with NRG, LA, Ob-R antagonist, or AG490 clearly alleviated HG-induced injuries and inflammation.
Conclusions:
This study provides new evidence of the NRG protective effects of H9c2 cells against HG-induced injuries possibly via modulation of the leptin-JAK2/STAT3 pathway.
Copyright: © 2019 Termedia & Banach.
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Endothelial Mineralocorticoid Receptor Ablation Confers Protection Towards Endothelial Dysfunction in Experimental Diabetes in Mice.
Acta Physiol (Oxf)2021 Sep;():e13731. doi: 10.1111/apha.13731.
Lyngsø Kristina S, Jensen Boye L, Hansen Pernille B L, Dimke Henrik,
Abstract
AIM:
With diabetes comes significant risk of macrovascular and microvascular complications. Circulating aldosterone levels increase in patients with diabetes. Aldosterone can directly affect vascular function via activation of the mineralocorticoid receptor (MR). We hypothesized that aldosterone via endothelial MR impairs endothelial function in a murine model of experimental diabetes.
METHOD:
Endothelial cell-specific mineralocorticoid receptor knockout MR ;Tie2-Cre mice (ECMR-KO) and wild-type FVB littermates were subjected to an experimental type-1 diabetic model by low dose streptozotocin injections (55mg/kg/day) for five consecutive days. After 10 weeks of diabetes, second-order mesenteric resistance arteries were perfused ex vivo to evaluate vessel contractility and endothelial function. The effect of ex vivo incubation with aldosterone with and without the antagonist, spironolactone was determined.
RESULTS:
Diabetic ECMR-KO and wild-type mice had similar, elevated, plasma aldosterone concentration while only diabetic wild-type mice displayed elevated urine albumin excretion and cardiac and kidney hypertrophy at 10 weeks. There were no differences in contraction (Emax and EC ) to thromboxane receptor agonist (U46619) and elevated K between groups. Wild-type diabetic mice showed impaired acetylcholine (ACh)-dependent relaxation, while diabetic ECMR-KO mice had intact ACh-mediated relaxation. Aldosterone incubation ex vivo impaired ACh mediated relaxation and rendered responses similar to diabetic WT arteries. Direct, ex vivo aldosterone effects were absent in ECMR-KO animals. Ex vivo inhibitory effects of aldosterone on endothelial relaxation in arteries from WT were abolished by spironolactone.
CONCLUSION:
These findings show that endothelial cell mineralocorticoid receptor activation accounts for diabetes-induced systemic endothelial dysfunction in experimental diabetes and may explain the cardiovascular protection by MR antagonists in diabetes.
This article is protected by copyright. All rights reserved.
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Affinity-based profiling of endogenous phosphoprotein phosphatases by mass spectrometry.
Nat Protoc2021 Sep;():. doi: 10.1038/s41596-021-00604-3.
Brauer Brooke L, Wiredu Kwame, Mitchell Sierra, Moorhead Greg B, Gerber Scott A, Kettenbach Arminja N,
Abstract
Phosphoprotein phosphatases (PPPs) execute >90% of serine/threonine dephosphorylation in cells and tissues. While the role of PPPs in cell biology and diseases such as cancer, cardiac hypertrophy and Alzheimer's disease is well established, the molecular mechanisms governing and governed by PPPs still await discovery. Here we describe a chemical proteomic strategy, phosphatase inhibitor beads and mass spectrometry (PIB-MS), that enables the identification and quantification of PPPs and their posttranslational modifications in as little as 12 h. Using a specific but nonselective PPP inhibitor immobilized on beads, PIB-MS enables the efficient affinity-capture, identification and quantification of endogenous PPPs and associated proteins ('PPPome') from cells and tissues. PIB-MS captures functional, endogenous PPP subunit interactions and enables discovery of new binding partners. It performs PPP enrichment without exogenous expression of tagged proteins or specific antibodies. Because PPPs are among the most conserved proteins across evolution, PIB-MS can be employed in any cell line, tissue or organism.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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Secretory products from epicardial adipose tissue induce adverse myocardial remodeling after myocardial infarction by promoting reactive oxygen species accumulation.
Cell Death Dis2021 Sep;12(9):848. doi: 10.1038/s41419-021-04111-x.
Hao Shuang, Sui Xin, Wang Jing, Zhang Jingchao, Pei Yu, Guo Longhui, Liang Zhenxing,
Abstract
Adverse myocardial remodeling, manifesting pathologically as myocardial hypertrophy and fibrosis, often follows myocardial infarction (MI) and results in cardiac dysfunction. In this study, an obvious epicardial adipose tissue (EAT) was observed in the rat model of MI and the EAT weights were positively correlated with cardiomyocyte size and myocardial fibrosis areas in the MI 2- and 4-week groups. Then, rat cardiomyocyte cell line H9C2 and primary rat cardiac fibroblasts were cultured in conditioned media generated from EAT of rats in the MI 4-week group (EAT-CM). Functionally, EAT-CM enlarged the cell surface area of H9C2 cells and reinforced cardiac fibroblast activation into myofibroblasts by elevating intracellular reactive oxygen species (ROS) levels. Mechanistically, miR-134-5p was upregulated by EAT-CM in both H9C2 cells and primary rat cardiac fibroblasts. miR-134-5p knockdown promoted histone H3K14 acetylation of manganese superoxide dismutase and catalase by upregulating lysine acetyltransferase 7 expression, thereby decreasing ROS level. An in vivo study showed that miR-134-5p knockdown limited adverse myocardial remodeling in the rat model of MI, manifesting as alleviation of cardiomyocyte hypertrophy and fibrosis. In general, our study clarified a new pathological mechanism involving an EAT/miRNA axis that explains the adverse myocardial remodeling occurring after MI.
© 2021. The Author(s).
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Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-?1 Signaling.
Pharmacology2021 Sep;():1-15. doi: 10.1159/000518464.
Chen Yong, He Ting, Zhang Zhongjun, Zhang Junzhi,
Abstract
INTRODUCTION:
Silent information regulator 1 (SIRT1) has been extensively investigated in the cardiovascular system and has been shown to play a pivotal role in mediating cell death/survival, energy production, and oxidative stress. However, the functional role of SIRT1 in pressure overload-induced cardiac hypertrophy and dysfunction remains unclear. Resveratrol (Rsv), a widely used activator of SIRT1, has been reported to protect against cardiovascular disease. We here examine whether activation of SIRT1 by Rsv attenuate pressure overload-induced cardiac hypertrophy and to identify the underlying molecular mechanisms.
METHODS:
In vivo, rat model of pressure overload-induced myocardial hypertrophy was established by abdominal aorta constriction (AAC) procedure. In vitro, Angiotensin II (Ang II) was applied to induce hypertrophy in cultured neonatal rat cardiomyocytes (NCMs). Hemodynamics and histological analyses of the heart were evaluated. The expression of SIRT1, transforming growth factor-?1 (TGF-?1)/phosphorylated (p)-small mother against decapentaplegic (Smad)3 and hypertrophic markers were determined by immunofluorescence, real-time PCR, and Western blotting techniques.
RESULTS:
In the current study, Rsv treatment improved left ventricular function and reduced left ventricular hypertrophy and cardiac fibrosis significantly in the pressure overload rats. The expression of SIRT1 was significantly reduced, while the expression of TGF-?1/p-Smad3 was significantly enhanced in AAC afflicted rat heart. Strikingly, treatment with Rsv restored the expressions of SIRT1 and TGF-?1/p-Smad3 under AAC influence. However, SIRT1 inhibitor Sirtinol (Snl) markedly prevented the effects of Rsv, which suggest that SIRT1 signaling pathway was involved in the cardiac protective effect of Rsv. In vitro studies performed in Ang II-induced hypertrophy in NCMs confirmed the cardiac protective effect of Rsv. Furthermore, the study presented that SIRT1 negatively correlated with the cardiac hypertrophy, cardiac fibrosis, and the TGF-?1/p-Smad3 expression.
CONCLUSIONS:
Taken together, these results indicated that activation of SIRT1 by Rsv attenuates cardiac hypertrophy, cardiac fibrosis, and improves cardiac function possibly via regulation of the TGF-?1/p-Smad3 signaling pathway. Our study may provide a potential therapeutic strategy for cardiac hypertrophy.
© 2021 S. Karger AG, Basel.
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Cardiac tamponade and massive pleural effusion in a young COVID-19-positive adult.
BMJ Case Rep2021 Sep;14(9):. doi: e244518.
Johny Dilip, Subramanyam Kodangala, Baikunje Nandakishore, Hosmane Giridhar Belur,
Abstract
COVID-19 has a broad spectrum of cardiac manifestations, and cardiac tamponade leading to cardiogenic shock is a rare presentation. A 30-year-old man with a history of COVID-19-positive, reverse transcription polymerase chain reaction (RT-PCR) done 1?week ago and who was home-quarantined, came to the emergency department with palpitations, breathlessness and orthopnoea. His ECG showed sinus tachycardia with low-voltage complexes, chest X-ray showed cardiomegaly and left pleural effusion and two-dimensional echocardiography showed large pericardial effusion with features suggestive of cardiac tamponade. He was taken up for emergency pericardiocentesis which showed haemorrhagic pericardial fluid. Intercostal drainage insertion was done for left-sided large pleural effusion. After ruling out all the other causes for haemorrhagic pericardial effusion, the patient was started on colchicine, steroids, ibuprofen and antibiotics to which he responded. Both pericardial and pleural effusions resolved completely on follow-up.
© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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Sleep-disordered breathing is independently associated with reduced atrial connexin 43 expression.
Heart Rhythm2021 Sep;():. doi: S1547-5271(21)02112-3.
Hegner Philipp, Lebek Simon, Tafelmeier Maria, Camboni Daniele, Schopka Simon, Schmid Christof, Maier Lars Siegfried, Arzt Michael, Wagner Stefan,
Abstract
BACKGROUND:
Patients with atrial fibrillation (AF) exhibit decreased atrial expression of connexin (Cx), which has been causally linked to a pro-arrhythmogenic substrate. Interestingly, patients with sleep-disordered-breathing (SDB) are at increased risk for AF, but the mechanisms remain unclear.
OBJECTIVE:
We tested the hypothesis that patients with SDB have reduced atrial connexin expression independent of important comorbidities.
METHODS:
We analyzed right atrial appendage biopsies from 77 patients undergoing coronary artery bypass grafting. Patients were tested for SDB by polygraphy before surgery. Expression of Cx40 and Cx43 mRNA were quantified using real-time qPCR and Western blot (Cx43). Structural atrial remodeling was investigated histologically and by qPCR. Postoperative AF was assessed by 12-lead ECG.
RESULTS:
Patients were stratified according to apnea-hypopnea-index (SDB if AHI?15/h, 32 vs. 45). Patients with SDB had significantly lower atrial Cx43 expression, which was negatively correlated with AHI and oxygen-desaturation-index. No significant increase in atrial fibrosis or expression of hypertrophy and inflammatory markers was observed. Interestingly, SDB remained the strongest independent predictor of decreased atrial Cx43 expression in a multivariate logistic regression model including age, gender, diabetes, and HFrEF, (odds ratio, OR, and confidence interval, CI: 7.58 (1.891-30.375), p=0.004). Moreover, the reduced atrial Cx43 expression was strongly associated with the occurrence of postoperative AF (OR 15.749 with CI 1.072-231.472, p=0.044).
CONCLUSION:
Patients with SDB exhibited decreased atrial Cx43 expression, which correlated with the severity of SDB. This correlation was independent of several concomitant diseases and may be linked to an increased risk of AF after cardiac surgery.
Copyright © 2021. Published by Elsevier Inc.
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The emerging role of miRNA-132/212 cluster in neurologic and cardiovascular diseases: Neuroprotective role in cells with prolonged longevity.
Mech Ageing Dev2021 Sep;():111566. doi: S0047-6374(21)00138-X.
El Fatimy Rachid, Boulaassafre Soukayna, Bouchmaa Najat, El Khayari Abdellatif, Vergely Catherine, Malka Gabriel, Rochette Luc,
Abstract
miRNA-132/212 are small regulators of gene expression with a function that fulfills a vital function in diverse biological processes including neuroprotection of cells with prolonged longevity in neurons and the cardiovascular system. In neurons, miRNA-132 appears to be essential for controlling differentiation, development, and neural functioning. Indeed, it also universally promotes axon evolution, nervous migration, plasticity as well is suggested as a neuroprotective against neurodegenerative diseases. Moreover, miRNA-132/212 disorder leads to neural developmental perturbation, and the development of degenerative disorders covering Alzheimer's, Parkinson's, and epilepsy's along with psychiatric perturbations including schizophrenia. Furthermore, the cellular mechanisms of the miRNA-132/212 have additionally been explored in cardiovascular diseases models. Also, the miRNA-132/212 family modulates cardiac hypertrophy and autophagy in cardiomyocytes. The protective and effective clinical promise of miRNA-132/212 in these systems is discussed in this review. To sum up, the current progress in innovative miRNA-based therapies for human pathologies seems of extreme concern and reveals promising novel therapeutic strategies.
Copyright © 2021. Published by Elsevier B.V.
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TFEB Insufficiency Promotes Cardiac Hypertrophy by Blocking Autophagic Degradation of GATA4.
J Biol Chem2021 Sep;():101189. doi: S0021-9258(21)00991-1.
Song Rui, Lei Han, Feng Li, Cheng Wanwen, Li Ying, Yao Ling Ling, Liu Jie,
Abstract
Autophagosome-lysosome pathway (ALP) insufficiency has been suggested to play a critical role in the pathogenesis of cardiac hypertrophy. However, the mechanisms underlying ALP insufficiency remain largely unknown, and strategies to specifically manipulate ALP insufficiency for treating cardiac hypertrophy are lacking. Transcription factor EB (TFEB), as a master regulator of ALP, regulates the generation and function of autophagosomes and lysosomes. We found TFEB was significantly decreased, while autophagosome markers were increased in phenylephrine (PE)- and transverse aortic constriction (TAC)-induced cardiomyocyte hypertrophy and failing hearts from patients with dilated cardiomyopathy. Knocking down TFEB induced ALP insufficiency, as indicated by increased autophagosome markers, decreased LC3II flux, and cardiomyocyte hypertrophy manifested through increased levels of atrial natriuretic peptide (ANP) and ?-myosin heavy chain 7 (?-MHC) and enlarged cell size. The effects of TFEB knockdown were abolished by promoting autophagy. TFEB overexpression improved autophagic flux and attenuated PE-stimulated cardiomyocyte hypertrophy and TAC-induced hypertrophic remodeling, fibrosis, and cardiac dysfunction. Curcumin analog compound C1, a specific TFEB activator, similarly attenuated PE-induced ALP insufficiency and cardiomyocyte hypertrophy. TFEB knockdown increased the accumulation of GATA4, a transcription factor for several genes causing cardiac hypertrophy by blocking autophagic degradation of GATA4, whereas knocking down GATA4 attenuated TFEB downregulation-induced cardiomyocyte hypertrophy. Both TFEB overexpression and C1 promoted GATA4 autophagic degradation and alleviated PE-induced cardiomyocyte hypertrophy. In conclusion, TFEB downregulation plays a vital role in the development of pressure overload-induced cardiac hypertrophy by causing ALP insufficiency and blocking autophagic degradation. Activation of TFEB represents a potential therapeutic strategy for treating cardiac hypertrophy.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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Right ventricular adaptation in pulmonary arterial hypertension
Orv Hetil2021 09;162(37):1485-1493. doi: 10.1556/650.2021.32171.
Csósza Györgyi, Lázár Zsófia, Rozgonyi Zsolt, Vágó Hajnalka, Losonczy György, Müller Veronika, Karlócai Kristóf,
Abstract
Összefoglaló. Pulmonalis artériás hypertoniában (PAH) a tüd?artériák falának átépülése az els?dleges patofiziológiai eltérés, amely a pulmonalis vascularis rezisztencia (PVR) és a pulmonalis nyomás progresszív emelkedéséhez vezet. Ez a nyomásemelkedés a jobb szívfélben az afterload fokozódásához vezet, ami hosszú távon jobbkamra-diszfunkciót és jobbszívfél-elégtelenséget okoz. Az egyre növekv? PVR mellett kialakuló cardialis adaptáció pontos patomechanizmusa nem ismert, de egyes betegek esetén nagyon eltér? lehet az adaptáció mértéke és kialakulásának üteme. A kialakuló myocardium-hypertrophia és -dilatáció mértéke nagyban függ a PAH etiológiájától, de emellett egyéb tényez?k - mint az életkor, a neurohumoralis aktiváció mértéke, genetikai és epigenetikai faktorok - is jelent?sen befolyásolják. Minél kevésbé képes a jobb kamra megtartani funkcióját az egyre növekv? ellenállással szemben, annál gyorsabban alakul ki a jobbszívfél-elégtelenség, és annál rosszabbak a beteg életkilátásai. Ezen folyamatok jobb megismerése klinikai jelent?séggel bír, mivel a jobb kamrai adaptáció el?segítése javíthatja a betegség kimenetelét. Orv Hetil. 2021; 162(37): 1485-1493. Summary. Remodeling of the pulmonary artery wall is the primary pathophysiological abnormality in pulmonary arterial hypertension leading to a progressive increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure. The elevation of pressure increases the afterload in the right heart, causing right ventricular dysfunction and right heart failure in the long term. The exact pathomechanism of cardiac adaptation with increasing PVR is unknown, but the degree and rate of adaptation may be very different in patients suffering from pulmonary hypertension. The development of myocardial hypertrophy and dilatation is highly dependent on the etiology of pulmonary hypertension, but is also significantly influenced by other factors such as age, degree of neurohumoral activation, and genetic and epigenetic factors. Right heart failure develops and life expectancy shortens if the right ventricle is unable to maintain its function in the face of increasing resistance. Orv Hetil. 2021; 162(37): 1485-1493.
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Clinical and pathological findings in rabbits with cardiovascular disease: 59 cases (2001-2018).
J Am Vet Med Assoc2021 Oct;259(7):764-776. doi: 10.2460/javma.259.7.764.
Ozawa Sarah, Guzman David Sanchez-Migallon, Keel Kevin, Gunther-Harrington Catherine,
Abstract
OBJECTIVE:
To determine epidemiological features of cardiovascular disease in rabbits examined at a veterinary teaching hospital and characterize clinical and pathological findings.
ANIMALS:
59 rabbits.
PROCEDURES:
Medical records from 2001 to 2018 were reviewed, and data were collected. Echocardiographic images and histologic diagnoses were reviewed.
RESULTS:
The prevalence of cardiovascular disease was 2.6% (59/2,249). Clinical signs related to cardiac disease included heart murmur (n = 25 rabbits), arrhythmia (22), tachypnea or dyspnea (13), hyporexia or anorexia (13), and muscle wasting (9). Radiographic (n = 39) abnormalities included cardiomegaly (19) and peritoneal (12) and pleural (11) effusion. Common echocardiographic (n = 37) diagnoses included degenerative valve disease (15), dilated cardiomyopathy (7), unclassified cardiomyopathy (4), restrictive cardiomyopathy (3), and hypertrophic cardiomyopathy (2). On ECG (n = 19), supraventricular arrhythmias (16) were more common than ventricular arrhythmias (12). Thirty-five necropsy reports were available, and diagnoses included cardiomyopathy (n = 14), myocarditis (10), and arteriosclerosis (9). Medical management (n = 20) included a wide range of drugs and dosages with few adverse effects. Survival times (n = 36 rabbits) ranged from 1 to 2,353 days with a median cardiac disease-specific survival time of 306 days.
CONCLUSIONS AND CLINICAL RELEVANCE:
The findings provided information on the prevalence of cardiovascular disease in rabbits and survival times for affected rabbits. Right-sided, left-sided, and biventricular congestive heart failure occurred equally. Median survival time was lower than that reported for other species. Further research on the diagnosis and treatment of cardiovascular disease in rabbits is needed.
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miR-337-5p promotes the development of cardiac hypertrophy by targeting Ubiquilin-1 (UBQLN1).
Bioengineered2021 Dec;12(1):6771-6781. doi: 10.1080/21655979.2021.1964892.
Ding Ying, Wang Jingyu, Lu Jun,
Abstract
Cardiac hypertrophy is an adaptive response of the myocardium to the pressure overload of the heart. MicroRNAs (miRNAs/miRs) are shown to be directly involved in the development of cardiac hypertrophy. However, the function of miR-337-5p and its potential contribution to the serine/threonine-protein kinase, a mammalian target of rapamycin (mTOR) signaling in cardiac hypertrophy remains unknown. In the present study, miR-337-5p expression was examined in cardiomyocytes treated with angiotensin II (Ang II). An adenovirus vector system was employed to knockdown miR-337-5p expression to investigate its functions in cardiac hypertrophy. The results revealed a significant increase in the expression of miR-337-5p in cardiomyocytes treated with Ang II as compared with controls. In addition, downregulation of miR-337-5p expression inhibited cardiac hypertrophy both and . Dual-luciferase reporter assays demonstrated Ubiquilin-1 ( as the direct target of miR-337-5p, and revealed its function in the modulation of mTOR signaling. Rescue experiments indicated that overexpression reversed the effects of miR-337-5p, and further verified this interaction. In summary, the results of the present study show that miR-337-5p silencing attenuates cardiac hypertrophy by targeting . Therefore, miR-337-5p plays a critical role in cardiac hypertrophy and may serve as a new therapeutic target.
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LOXL2 Inhibitor Attenuates Angiotensin II-Induced Atrial Fibrosis and Vulnerability to Atrial Fibrillation through Inhibition of Transforming Growth Factor Beta-1 Smad2/3 Pathway.
Cerebrovasc Dis2021 Sep;():1-11. doi: 10.1159/000518526.
Wu Yingbiao, Can Jin, Hao Shuwen, Qiang Xun, Ning Zhongping,
Abstract
OBJECTIVES:
Angiotensin II (Ang II)-induced atrial fibrosis plays a vital role in the development of atrial fibrillation (AF). Lysyl oxidase-like 2 (LOXL2) plays an essential role in matrix remodeling and fibrogenesis, indicating it may involve fibrosis-associated diseases. This study aims to elucidate the role of LOXL2 in AF, and its specific inhibitor can suppress Ang II-induced inflammatory atrial fibrosis and attenuate the enhanced vulnerability to AF.
METHODS:
Male mice C57BL/6 were subcutaneously infused with either saline or Ang II (2 mg/kg/day) for 4 weeks. DMSO or LOXL2 inhibitor LOXL2-IN-1 hydrochloride (LOXL2-IN-1) at a dose of 100 ?g/kg/day were intraperitoneally injected once daily for 4 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced by transesophageal burst pacing in vivo.
RESULTS:
Expression of LOXL2 was increased in serum of AF patients and Ang II-treated mice. LOXL2-IN-1 significantly attenuated Ang II-induced AF vulnerability, cardiac hypertrophy, atrial inflammation, and fibrosis. LOXL2-IN-1 suppressed Ang II-induced expression of transforming growth factor beta-1 (TGF-?1) and collagen I and phosphorylation of Smad2/3 in atrial tissue.
CONCLUSIONS:
LOXL2 is a target of AF, and its inhibitor prevents atrial fibrosis and attenuated enhanced vulnerability to AF potentially through the TGF-?/Smad pathway.
© 2021 S. Karger AG, Basel.
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The Association of Morning Hypertension With Target Organ Damage in Patients With Chronic Kidney Disease and Hypertension.
Front Cardiovasc Med2021 ;8():715491. doi: 10.3389/fcvm.2021.715491.
Liu Xiang, Li Fangming, Zhang Ting, Zheng Zhiyao, Zhou Huan, Qin Aiya, Tang Yi, Qin Wei,
Abstract
To determine the association between morning hypertension and target organ damage (TOD) in patients with chronic kidney disease (CKD) and hypertension. In this cross-sectional study, 447 patients with CKD and hypertension from two centers were enrolled. Ambulatory blood pressure monitoring was conducted in all patients. Linear regression and logistic regression analysis were used to determine the association between morning hypertension and TOD in patients with CKD and hypertension, including assessments of estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), urine protein/creatinine ratio (UPCR), and left ventricular hypertrophy (LVH). Overall, 194 (43.4%) participants had morning hypertension. Morning hypertension was strongly correlated with LVH [odds ratio (OR), 2.14; 95% confidence interval (CI), 1.3-3.51;
Copyright © 2021 Liu, Li, Zhang, Zheng, Zhou, Qin, Tang and Qin.
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Association of Maternal Gestational Weight Gain With Left Ventricle Geometry and Function in Offspring at 4 Years of Age: A Prospective Birth Cohort Study.
Front Pediatr2021 ;9():722385. doi: 10.3389/fped.2021.722385.
Wang Jian, Du Bowen, Wu Yujian, Li Zhuoyan, Chen Qian, Zhang Xi, Zhang Lin, Ye Yujiao, Wu Yurong, Chen Sun, Sun Kun,
Abstract
Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change. Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (? 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age. Interventricular septal thickness during diastole had a significantly positive correlation with total GWG [? = 0.009, (0.001, 0.017)]. In the second and third trimesters, LV mass index [? = 0.149, (0.015,0.282)], interventricular septal thickness in systole [? = 0.027, (0.011,0.043)], and in diastole [? = 0.014, (0.005,0.023)] were positively associated with GWG. The risks of eccentric [OR = 1.115, (1.232, 1.010)] and concentric hypertrophy [OR = 1.133, (1.259,1.018)] increased with the elevation of maternal GWG. This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring.
Copyright © 2021 Wang, Du, Wu, Li, Chen, Zhang, Zhang, Ye, Wu, Chen and Sun.
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Prognostic Model of Typical Complications Caused by Transcatheter Aortic Valve Replacement.
Sovrem Tekhnologii Med2020 ;12(2):27-32. doi: 10.17691/stm2020.12.2.03.
Ovcharenko E A, Klyshnikov K U, Ganyukov V I, Shilov A A, Vereshchagin I E, Sizova I N, Tarasov R S, Barbarash L S,
Abstract
was to develop a prognostic model based on statistical discriminant analysis to assess the risk of postoperative disturbance of cardiac conduction and paraprosthetic regurgitation after transcatheter aortic valve replacement.
Materials and Methods:
Clinical data of 10 patients implanted with CoreValve prostheses (Medtronic Inc., USA) were used to develop prognostic models. To that end, we analyzed changes in hemodynamic and functional parameters provided by echocardiography in the pre- and postoperative periods.
Results:
We observed significant positive changes in the severity of left ventricular myocardial hypertrophy; on the contrary, volume indicators did not significantly change, which might be associated with the concentric type of left ventricular hypertrophy. The discriminant analysis made it possible to determine major (preoperative) morphological and functional indicators associated with the two most common complications of the procedure: left bundle branch block and paraprosthetic regurgitation. Left ventricular posterior wall thickness, interventricular septal thickness, left atrium dimension, and myocardial mass are the critical factors that determine the development of these complications.
Conclusion:
In the prognostic model, the proposed weighting coefficients allow one to assess the risk of postoperative complications; however, the presence of false-positive results requires further refinement of these coefficients within the linear equation.
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Cardiac changes in infants of diabetic mothers.
World J Diabetes2021 Aug;12(8):1233-1247. doi: 10.4239/wjd.v12.i8.1233.
Al-Biltagi Mohammed, El Razaky Osama, El Amrousy Doaa,
Abstract
Diabetes mellitus (DM) is a systemic chronic metabolic disorder characterized by increased insulin resistance and/or ?- cell defects. It affects all ages from the foetal life, neonates, childhood to late adulthood. Gestational diabetes is a critical risk factor for congenital heart diseases (CHDs). Moreover, the risk increases with low maternal education, high body mass index at conception, undiagnosed pre-gestational diabetes, inadequate antenatal care, improper diabetes control, and maternal smoking during pregnancy. Maternal DM significantly affects the foetal heart and foetal-placental circulation in both structure and function. Cardiac defects, myocardial hypertrophy are three times more prevalent in infants of diabetic mothers (IDMs). Antenatal evaluation of the cardiac function and structures can be performed with foetal electrocardiography and echocardiography. Postnatal cardiac evaluation can be performed with natal and postnatal electrocardiography and echocardiography, detection of early atherosclerotic changes by measuring aortic intima-media thickness, and retinal vascular changes by retinal photography. Ameliorating the effects of diabetes during pregnancy on the offspring depends mainly on pregestational and gestational diabetes prevention. However, other measures to reduce the risk, such as using medications, nutritional supplements, or probiotics, still need more research. This review discusses the mechanism of foetal sequels and the risk factors that increase the prevalence of CHDs in gestational DM, the various cardiac outcomes of gestational DM on the foetus and offspring, cardiac evaluation of foetuses and IDMs, and how to alleviate the consequences of gestational DM on the offspring.
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
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An indolent cause of high-output heart failure in end-stage kidney disease-Application of the Nicoladoni-Israel-Branham test: A case report.
Echocardiography2021 Sep;():. doi: 10.1111/echo.15195.
Ogugua Fredrick, Herzog Charles A, Sahadevan Meena, Davies Scott, Shroff Gautam R,
Abstract
BACKGROUND:
A hemodynamically significant arteriovenous fistula (AVF) in end-stage kidney disease (ESKD) causes a high flow state, resulting in pathologic cardiovascular remodeling, and deserves timely clinical recognition.
CASE:
A 55-year-old woman with history of ESKD with deceased donor kidney transplant with failing graft function and baseline creatinine of 2.8 mg/dl presented to the clinic with nocturnal cough, orthopnea, dyspnea on exertion and pedal edema. Physical exam was notable for large, aneurysmal right brachial AVF. Transthoracic echocardiography (TTE) revealed left ventricular (LV) enlargement and hypertrophy and elevated cardiac output (CO) of 10 L/min, raising a clinical concern for high-output heart failure.
DECISION MAKING:
A non-invasive assessment of the hemodynamic significance of the AVF was performed using a TTE. During temporary occlusion of the AVF, it was determined that about 27% of the resting CO was attributed to the AVF, suggesting hemodynamic significance. Nicoladoni-Israel-Branham sign was negative as there was no change in patient's heart rate, but this was potentially attributed to beta-blockade and chronic loading conditions. She underwent AVF banding and 2-month later her presenting symptoms resolved, and a TTE showed a decrease in resting CO of 7.6 L/min with normalization of LV size.
CONCLUSION:
This case highlights several teaching points. Firstly, in patients with ESKD, a large AVF can contribute to a high CO state resulting in maladaptive cardiovascular remodeling. Secondly, TTE evaluation of the hemodynamic contribution of an AVF can be performed with the application of the Nicoladoni-Israel-Branham sign. Finally, some experts recommend pre-emptive banding or ligation of AVF after successful kidney transplantation as this has been shown to have symptomatic and cardiovascular benefits.
© 2021 Wiley Periodicals LLC.
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Hypothyroid cardiomyopathy: A reversible phenocopy of hypertrophic cardiomyopathy.
Echocardiography2021 Sep;():. doi: 10.1111/echo.15183.
Cianciulli Tomás F, Morita Luis A, Saccheri María C, Zylberman Marcelo,
Abstract
We present the case of a 46-year-old patient with hypothyroidism secondary to Hashimoto's thyroiditis who was admitted with decompensation in the form of myxedema. A 2-D echocardiogram shows a septal asymmetric hypertrophy, with low-voltage QRS complex in the ECG and a bull's-eye map of longitudinal strain with preserved apical strain with reduction of mid and basal strain that results in "cherry on the top" pattern, similar to the most frequent phenocopy of hypertrophic cardiomyopathy, as is the cardiac amyloidosis, and that, unlike this pathology, reverted after the patient reached the euthyroid state.
© 2021 Wiley Periodicals LLC.
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