Chronic cold exposure causes left ventricular hypertrophy that appears to be physiological DOI Creative Commons
McKenna P. A. Burns, Caroline R. Reges, Spencer Barnhill

et al.

Journal of Experimental Biology, Journal Year: 2024, Volume and Issue: 227(20)

Published: Aug. 29, 2024

ABSTRACT Exposure to winter cold causes an increase in energy demands meet the challenge of thermoregulation. In small rodents, this cardiac output leads a profound hypertrophy, 2–3 times that typically seen with exercise training. The nature hypertrophy and its relevance mortality remains unclear. Our goal was characterize cold-induced assess similarity either exercise-induced (physiological) or pathological hypertension. We hypothesized will most closely resemble but be another unique pathway for physiological growth. found largely reversed after return warm temperatures. Further, metabolic rates were elevated while gene expression mitochondrial enzyme activities indicative pathology absent. A panel comparing hearts exercised cold-exposed mice further suggests these are similar, although not identical. conclusion, we chronic led phenotype resembled enhanced rate, without induction fetal genes, decreased genes associated fatty acid oxidation, suggesting heart failure is cause rodents identifying novel approach study

Language: Английский

Astragali Radix−Notoginseng Radix et Rhizoma medicine pair prevents cardiac remodeling by improving mitochondrial dynamic balance DOI

Pingping Lin,

Hong Chen,

Zekun Cui

et al.

Chinese Journal of Natural Medicines, Journal Year: 2025, Volume and Issue: 23(1), P. 54 - 63

Published: Jan. 1, 2025

Language: Английский

Citations

1
Logic-based machine learning predicts how escitalopram attenuates cardiomyocyte hypertrophy DOI Creative Commons
Taylor G. Eggertsen, Joshua G. Travers, Elizabeth J. Hardy

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(10)

Published: March 4, 2025

Cardiomyocyte hypertrophy is a key clinical predictor of heart failure. High-throughput and AI-driven screens have the potential to identify drugs downstream pathways that modulate cardiomyocyte hypertrophy. Here, we developed LogiRx, logic-based mechanistic machine learning method predicts drug-induced pathways. We applied LogiRx discover how discovered in previous compound screen attenuate experimentally validated predictions neonatal cardiomyocytes, adult mice, two patient databases. Using predicted antihypertrophic for seven currently used treat noncardiac disease. escitalopram (Lexapro) mifepristone inhibit cultured cardiomyocytes contexts. The model prevents through an “off-target” serotonin receptor/PI3Kγ pathway, mechanistically using additional investigational drugs. Further, reduced mouse fibrosis. Finally, mining both FDA University Virginia databases showed patients with depression on lower incidence cardiac than those prescribed other reuptake inhibitors do not target receptor. Mechanistic by discovers drug perturb cell states, which may enable repurposing limit remodeling off-target

Language: Английский

Citations

1
Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis DOI Creative Commons

Evangelia Beslika,

Adelino Leite‐Moreira, León J. De Windt

et al.

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(5), P. 461 - 475

Published: Feb. 29, 2024

Abstract Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis (AS). AS known to increase the pressure load left ventricle, causing compensative response muscle, which progressively will lead dilation and heart failure. At cellular level, this corresponds considerable in size cardiomyocytes, as cardiomyocyte hypertrophy, while their proliferation capacity attenuated upon first developmental stages. Cardiomyocytes, order cope with increased workload (overload), suffer alterations morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity, cell death mechanisms. Moreover, modifications niche, involving inflammation, immune infiltration, fibrosis, angiogenesis, contribute subsequent events pathologic hypertrophic response. Considering emerging need for better understanding condition treatment improvement, only available option consists surgical interventions at late stage disease, when muscle state irreversible, large animal models have been developed mimic human condition, greatest extend. Smaller lack physiological, molecular mechanisms that sufficiently resemblance humans vitro techniques yet fail provide adequate complexity. Animals, such ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries), porcine (pig, Sus scrofa), contributed research by elucidating implicated condition. Essential discoveries each model are reported discussed briefly review. Results experimentation could further be interpreted aiming prevention disease progress or, alternatively, regression physiologic state. This review summarizes important aspects pathophysiology LV applied currently

Language: Английский

Citations

7
Pterostilbene attenuates heart failure by inhibiting myocardial ferroptosis through SIRT1/GSK-3β/GPX4 signaling pathway DOI Creative Commons
Fan Zhang, Zhuanglin Zeng, Jiahui Zhang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e24562 - e24562

Published: Jan. 21, 2024

Sustained myocardial injury due to hypertension and diabetes mellitus leads production of endogenous reactive oxygen species (ROS) insufficient antioxidant capacity, increasing the risk cardiomyocyte ferroptosis. Ferroptosis is a nonapoptotic form cell death driven by unrestricted lipid peroxidation. Dysfunction glutathione peroxidase 4 (GPX4) system also plays an important role in Cardiomyocyte ferroptosis ultimately deterioration, such as inflammation, fibrosis, cardiac remodeling, resulting structural functional changes. Pterostilbene (PTS), demethylated derivative resveratrol, exhibits strong anti-inflammatory antioxidative activities. In this study, we used vitro experiments explore induced angiotensin II (Ang II) primary myocytes (CMs) vivo prepare transverse aortic constriction (TAC)-induced dysfunction mouse model. PTS can significantly ameliorate Ang II-induced reduce while improving function mice after TAC vivo. Further mechanistic investigations revealed that exerts its protective effect through SIRT1/GSK-3β/GPX4 pathway. After siRNA-mediated knockdown SIRT1 or GPX4 CMs, effects on cardiomyocytes were abolished. This study provides theoretical support for potential attenuate pathological remodeling heart failure preliminary exploration molecular pathways involved mechanism.

Language: Английский

Citations

5
Syringaldehyde Alleviates Cardiac Hypertrophy Induced by Hyperglycemia in H9c2 Cells Through GLP-1 Receptor Signals DOI Creative Commons
Yingxiao Li,

Chao-Tien Hsu,

Tingting Yang

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 110 - 110

Published: Jan. 16, 2025

Background: Cardiac hypertrophy is a significant complication of diabetes, often triggered by hyperglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists alleviate cardiac hypertrophy, but their efficacy diminishes under GLP-1 resistance. Syringaldehyde (SA), natural phenolic compound, may activate receptors and mitigate hypertrophy. This study explores SA's therapeutic potential in hyperglycemia-induced H9c2 cardiomyocytes. Methods: cells were exposed to high glucose induce Cells treated with varying SA concentrations, hypertrophic biomarkers analyzed using ELISA, qPCR, Western blot. Results: reduced cell size dose-dependent manner while increasing expression cAMP levels. These effects attenuated GLP-1-resistant cells, highlighting the role activation. AMPK activation was essential, as its inhibition abolished effects. also decreased O-linked N-acetylglucosamine transferase (OGT) via activation, contributing Conclusions: alleviates activating signaling pathway.

Language: Английский

Citations

0
Targeting senescence and GATA4 in age-related cardiovascular disease: a comprehensive approach DOI
Mohd Imran, Abdulmalik Saleh Alfawaz Altamimi, Muhammad Afzal

et al.

Biogerontology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 20, 2025

Language: Английский

Citations

0
Heart-on-a-chip: a revolutionary organ-on-chip platform for cardiovascular disease modeling DOI Creative Commons

Beiqin Liu,

Shuyue Wang,

Hong Ma

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 30, 2025

Heart-on-a-chip (HoC) devices have emerged as a powerful tool for studying the human heart's intricate functions and dysfunctions in vitro. Traditional preclinical models, such 2D cell cultures model animal model, limitations accurately predicting response to cardiovascular diseases treatments. The HoC approach addresses these shortcomings by recapitulating microscale anatomy, physiology, biomechanics of heart, thereby providing more clinically relevant platform drug testing, disease modeling, personalized therapy. Recent years seen significant strides technology, driven advancements biomaterials, bioelectronics, tissue engineering. Here, we first review construction on-chip detection HoC. Then introduce current proceedings vitro models (CVD) based on platform, including ischemia myocardial infarction, cardiac fibrosis, scar, hypertrophy other CVD models. Finally, discuss future directions related emerging technologies.

Language: Английский

Citations

0
Novel therapeutic insights into pathological cardiac hypertrophy: tRF-16-R29P4PE regulates PACE4 and metabolic pathways DOI

Feng Wang,

Ping Li, Xinxin Yan

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 119920 - 119920

Published: Feb. 1, 2025

Language: Английский

Citations

0
17-beta estradiol prevents cardiac myocyte hypertrophy by regulating mitochondrial E3 ubiquitin ligase 1 DOI Creative Commons
Ximena Calle, Valeria Garrido‐Moreno, Brenda Becerra

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 19, 2025

Abstract Cardiac hypertrophy is a cellular process characterized by the increased size of cardiomyocytes in response to high workload or stress. 17-beta estradiol (E2) has cardioprotective and anti-hypertrophic effects maintaining mitochondrial network function. MUL1 ubiquitin ligase directly involved control fission mitophagy. Studies from our group others have previously shown that cardiomyocyte associated with dysfunction. These findings led us study vitro whether E2 regulates prevent cardiac hypertrophy, fission, dysfunction induced catecholamine norepinephrine (NE). Our results showed NE induces cultured rat cardiomyocytes. Pre-treatment (10-100 nM) prevented NE-dependent increases cell perimeter hypertrophic stress markers ANP BNP at both protein mRNA levels. fragmentation reduced ATP levels, were E2. In s ilico analysis suggested putative binding site for estrogen receptors on gene promoter. accordance this finding, levels NE. data also siRNA knockdown counteracted NE-induced dysfunction, mirroring protective effect triggered contrast, adenovirus did not protection hypertrophy. Further, vivo transgenic mouse model overexpressing revealed only young male mice overexpressed protein. Consequently, they exhibited marker ANP, an elevated heart weight, larger size. Therefore, demonstrate prevents myocyte regulating MUL1.

Language: Английский

Citations

0
Baicalin Prevents Chronic β‐AR Agonist‐Induced Heart Failure via Preventing Oxidative Stress and Overactivation of the NADPH Oxidase NOX2 DOI Creative Commons

Yixuan Ge,

En Ma,

Xinxin Guo

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 1, 2025

ABSTRACT Heart failure (HF) remains the leading cause of mortality worldwide. Although various drugs are currently used in treatment HF, including angiotensin receptor blockers, angiotensin‐converting enzyme inhibitors and beta none these can reverse physiological remodelling heart associated with HF. Therefore, discovering novel that limit extent HF or prevent structural dysfunction during progression is urgently needed. Baicalin a natural flavonoid widely Traditional Chinese Medicine for its anti‐inflammatory anti‐oxidative effects; however, role baicalin chronic particular underlying mechanisms action, largely unelucidated. Murine models beta‐adrenergic agonist (β‐AR)‐induced were induced via induction isoproterenol (ISO) 4 weeks. Furthermore, we examined effects protecting against ISO‐induced cardiac impairment Daily administrations robustly protected pathophysiological changes heart, hypertrophy, reduced ejection fraction, fibrosis remodelling. also strongly inhibited production reactive oxygen nitrogen species by preventing overactivation NADPH oxidase NOX2. Hence, cardioprotective β‐AR‐induced due to NOX2 generation excessive oxidative stress. Our findings provide new mechanistic insight suggest therapeutic potential as drug

Language: Английский

Citations

0