Cardiomyocyte maturation alters molecular stress response capacities and determines cell survival upon mitochondrial dysfunction DOI Creative Commons

Nina Schraps,

Michaela Tirre,

Simon Pyschny

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 213, P. 248 - 265

Published: Jan. 22, 2024

Cardiomyocyte maturation during pre- and postnatal development requires multiple intertwined processes, including a switch in energy generation from glucose utilization the embryonic heart towards fatty acid oxidation after birth. This is accompanied by boost mitochondrial mass to increase capacities for oxidative phosphorylation ATP required efficient contraction. Whether cardiomyocyte differentiation paralleled augmented deal with reactive oxygen species (ROS), physiological byproducts of electron transport chain (ETC), less clear. Here we show that expression genes proteins involved redox homeostasis protein quality control within mitochondria increases birth mouse human heart. Using primary embryonic, neonatal adult cardiomyocytes vitro investigated how excessive ROS production induced dysfunction affects cell survival stress response at different stages maturation. Embryonic largely tolerate inhibition ETC complex III antimycin A (AMA) as well synthase (complex V) oligomycin but are susceptible I rotenone. All three inhibitors alter intracellular distribution ultrastructure cardiomyocytes. In contrast, treated AMA undergo rapid morphological changes cellular disintegration. At molecular level activate antioxidative defense mechanisms, integrated (ISR) ER not unfolded upon inhibition. fail ISR following treatment. conclusion, our results identified fundamental differences differentiated compared immature subjected dysfunction. The high tolerance might allow outlasting unfavorable intrauterine conditions thereby preventing fetal or perinatal disease may contribute regenerative capacity mammalian

Language: Английский

Transfer learning enables predictions in network biology DOI
Christina V. Theodoris, Ling Xiao,

Anant Chopra

et al.

Nature, Journal Year: 2023, Volume and Issue: 618(7965), P. 616 - 624

Published: May 31, 2023

Language: Английский

Citations

393
Mitochondrial dysfunction in human hypertrophic cardiomyopathy is linked to cardiomyocyte architecture disruption and corrected by improving NADH-driven mitochondrial respiration DOI Creative Commons
Edgar E. Nollet, Inez Duursma,

Anastasiya Rozenbaum

et al.

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(13), P. 1170 - 1185

Published: Jan. 12, 2023

Abstract Aims Genetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs the absence a mutation genotype-negative Mitochondrial dysfunction thought to be key driver pathological remodelling HCM. Reports mitochondrial respiratory function and specific disease-modifying treatment options patients with are scarce. Methods results Respirometry was performed on septal myectomy tissue from (n = 59) evaluate oxidative phosphorylation fatty acid oxidation. most notably reflected impaired NADH-linked respiration. but not respiration markedly depressed indexed thickness ≥10 compared <10. explained reduced abundance or fragmentation mitochondria, as evaluated transmission electron microscopy. Rather, improper organization mitochondria relative myofibrils (expressed percentage disorganized mitochondria) strongly associated dysfunction. Pre-incubation cardiolipin-stabilizing drug elamipretide raising NAD+ levels both boosted Conclusion cardiomyocyte architecture disruption linked hypertrophy Despite severe myocardial were responsive treatments aimed at restoring function, eliciting target prevent ameliorate cardiac disease Mitochondria-targeting therapy may particularly benefit HCM, given tight link between impairment thickening this subpopulation.

Language: Английский

Citations

53
Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease DOI Creative Commons
María Camacho Encina, Laura Booth, Rachael Redgrave

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 353 - 353

Published: Feb. 17, 2024

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are primary cause death worldwide, with an immense impact on patient quality life and disability. According to World Health Organization, CVD takes estimated 17.9 million lives each year, where more than four out five deaths due attacks strokes. In decades come, increased prevalence age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular disease, failure (HF) will contribute even greater health economic burden global average expectancy increases consequently world’s population continues age. Considering this, it is important focus our research efforts understanding fundamental mechanisms underlying CVD. this review, we cellular senescence mitochondrial dysfunction, which have long been established We also assess recent advances in targeting dysfunction including energy starvation oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, therapies that influence both therefore perhaps represent strategies most clinical potential, range, utility.

Language: Английский

Citations

22
Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction DOI Open Access
Huabo Zheng, Yichen Xu, Elisa A. Liehn

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3114 - 3114

Published: March 7, 2024

Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, an ischemic insult sudden oxygen exposure lead exacerbated synthesis additional reactive oxidative species persistence increased oxidation levels. Attempts based on antioxidant treatment have failed achieve effective therapy for cardiovascular disease patients. The controversial use vitamin C as clinical practice is comprehensively systematized discussed this review. dose-dependent adsorption release kinetics mechanism complex; however, review may provide holistic perspective its potential preventive supplement and/or combined precise targeted therapeutics management therapy.

Language: Английский

Citations

21
Mitochondrial Ca2+ Signaling in Health, Disease and Therapy DOI Creative Commons
Lorenzo Modesti, Alberto Danese, Veronica Angela Maria Vitto

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1317 - 1317

Published: May 25, 2021

The divalent cation calcium (Ca2+) is considered one of the main second messengers inside cells and acts as most prominent signal in a plethora biological processes. Its homeostasis guaranteed by an intricate complex system channels, pumps, exchangers. In this context, regulating cellular Ca2+ levels, mitochondria control both uptake release Ca2+. Therefore, at mitochondrial level, plays dual role, participating vital physiological processes (ATP production regulation metabolism) pathophysiological (cell death, cancer progression metastasis). Hence, it not surprising that alterations (mCa2+) pathways or mutations transporters affect activities functions entire cell. Indeed, widely recognized dysregulation mCa2+ signaling leads to various pathological scenarios, including cancer, neurological defects cardiovascular diseases (CVDs). This review summarizes current knowledge on homeostasis, related mechanisms significance physiology human diseases. We also highlight strategies aimed remedying promising therapeutical approaches.

Language: Английский

Citations

82
Calcium dysregulation in heart diseases: Targeting calcium channels to achieve a correct calcium homeostasis DOI
Giampaolo Morciano, Alessandro Rimessi, Simone Patergnani

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 177, P. 106119 - 106119

Published: Feb. 5, 2022

Language: Английский

Citations

41
Mitochondrial quality control in health and cardiovascular diseases DOI Creative Commons
Asli E. Atici, Timothy R. Crother, Magali Noval Rivas

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Nov. 6, 2023

Cardiovascular diseases (CVDs) are one of the primary causes mortality worldwide. An optimal mitochondrial function is central to supplying tissues with high energy demand, such as cardiovascular system. In addition producing ATP a power source, mitochondria also heavily involved in adaptation environmental stress and fine-tuning tissue functions. Mitochondrial quality control (MQC) through fission, fusion, mitophagy, biogenesis ensures clearance dysfunctional preserves homeostasis tissues. Furthermore, generate reactive oxygen species (ROS), which trigger production pro-inflammatory cytokines regulate cell survival. dysfunction has been implicated multiple CVDs, including ischemia-reperfusion (I/R), atherosclerosis, heart failure, cardiac hypertrophy, hypertension, diabetic genetic cardiomyopathies, Kawasaki Disease (KD). Thus, MQC pivotal promoting health. Here, we outline mechanisms discuss current literature on CVDs.

Language: Английский

Citations

25
LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2 DOI Creative Commons

Xiang Nie,

Jiahui Fan, Dai B

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 134(4), P. 425 - 441

Published: Feb. 1, 2024

Human cardiac long noncoding RNA (lncRNA) profiles in patients with dilated cardiomyopathy (DCM) were previously analyzed, and the CHKB (choline kinase beta) divergent transcript (CHKB-DT) levels found to be mostly downregulated heart. In this study, function of CHKB-DT DCM was determined.

Language: Английский

Citations

15
Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation DOI Creative Commons
Yeranuhi Hovhannisyan, Zhenlin Li, Domitille Callon

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Beyond the observed alterations in cellular structure and mitochondria, mechanisms linking rare genetic mutations to development of heart failure patients affected by desmin remain unclear due part, lack relevant human cardiomyocyte models.

Language: Английский

Citations

9
Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy DOI Open Access
Yuliang Feng,

Liuyang Cai,

Wanzi Hong

et al.

Circulation, Journal Year: 2022, Volume and Issue: 145(22), P. 1663 - 1683

Published: April 11, 2022

Transcriptional reconfiguration is central to heart failure, the most common cause of which dilated cardiomyopathy (DCM). The effect 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive.

Language: Английский

Citations

36