Endothelial dysfunction: molecular mechanisms and clinical implications

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 22, 2024

Abstract Cardiovascular disease (CVD) and its complications are a leading cause of death worldwide. Endothelial dysfunction plays crucial role in the initiation progression CVD, serving as pivotal factor pathogenesis cardiovascular, metabolic, other related diseases. The regulation endothelial is influenced by various risk factors intricate signaling pathways, which vary depending on specific context. Despite numerous research efforts aimed at elucidating mechanisms underlying dysfunction, precise molecular pathways involved remain incompletely understood. This review elucidates recent findings pathophysiological including nitric oxide availability, oxidative stress, inflammation‐mediated pathways. We also discuss impact pathological conditions, atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, neurodegenerative Furthermore, we summarize traditional novel potential biomarkers well pharmacological nonpharmacological therapeutic strategies for protection treatment CVD complications. Consequently, this to improve understanding emerging approaches reducing developing associated complications, mitigating dysfunction.

Language: Английский

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Reactive oxygen species in hypertension

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Language: Английский

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Role of Argininosuccinate Synthase 1 ‐Dependent L‐Arginine Biosynthesis in the Protective Effect of Endothelial Sirtuin 3 Against Atherosclerosis

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 17, 2024

Abstract Atherosclerosis is initiated with endothelial cell (EC) dysfunction and vascular inflammation under hyperlipidemia. Sirtuin 3 (SIRT3) a mitochondrial deacetylase. However, the specific role of SIRT3 during atherosclerosis remains poorly understood. The present study aims to mechanism in EC function atherosclerosis. Wild‐type Sirt3f/f mice endothelium‐selective knockout Sirt3f/f; Cdh5Cre/+ (Sirt3 EC‐KO ) are injected adeno‐associated virus (AAV) overexpress PCSK9 fed high‐cholesterol diet (HCD) for 12 weeks induce Sirt3 exhibit increased atherosclerotic plaque formation, along elevated macrophage infiltration, inflammation, reduced circulating L‐arginine levels. In human ECs, inhibition resulted heightened nitric oxide (NO) production, reactive oxygen species (ROS), diminished Silencing results hyperacetylation deactivation Argininosuccinate Synthase 1 (ASS1), rate‐limiting enzyme involved biosynthesis, this effect abolished mutant ASS1. Furthermore, supplementation attenuates enhanced formation mice. This provides compelling evidence supporting protective also suggests critical SIRT3‐induced deacetylation ASS1 by ECs arginine synthesis.

Language: Английский

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Roles of Sirtuins in Cardiovascular Diseases: Mechanisms and Therapeutics

Circulation Research, Journal Year: 2025, Volume and Issue: 136(5), P. 524 - 550

Published: Feb. 27, 2025

Cardiovascular diseases (CVDs) are experiencing a rapid surge and widely recognized as the leading cause of mortality in current aging society. Given multifactorial etiology CVDs, understanding intricate molecular cellular mechanisms is imperative. Over past 2 decades, many scientists have focused on Sirtuins, family nicotinamide adenine dinucleotide–dependent deacylases. Sirtuins highly conserved across species, from yeasts to primates, play crucial role linking diseases. participate nearly all key physiological pathological processes, ranging embryogenic development stress response aging. Abnormal expression activity exist aging-related diseases, while their activation has shown efficacy mitigating these (eg, CVDs). In terms research, this field maintained fast, sustained growth recent years, fundamental studies clinical trials. review, we present comprehensive, up-to-date discussion biological functions roles regulating cardiovascular biology CVDs. Furthermore, highlight latest advancements utilizing Sirtuin-activating compounds dinucleotide boosters potential pharmacological targets for preventing treating The unresolved issues field—from chemicobiological regulation Sirtuin-targeted CVD investigations—are also discussed. This timely review could be critical updated knowledge Sirtuin CVDs facilitating accessibility Sirtuin-targeting interventions.

Language: Английский

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SirT3 activates AMPK-related mitochondrial biogenesis and ameliorates sepsis-induced myocardial injury

Aging, Journal Year: 2020, Volume and Issue: 12(16), P. 16224 - 16237

Published: July 28, 2020

Sirtuin-3 (SirT3) and AMPK stimulate mitochondrial biogenesis, which increases turnover cardiomyocyte regeneration. We studied the effects of SirT3, AMPK, biogenesis on sepsis-induced myocardial injury. Our data showed that after treating cardiomyocytes with lipopolysaccharide, SirT3 levels decreased, this was followed by dysfunction death. Overexpression activated pathway improved is required to sustain redox balance, maintain respiration, suppress apoptosis. Inhibition abolished SirT3/AMPK-induced cardioprotection causing damage. These findings indicate reduces injury activating AMPK-related biogenesis.

Language: Английский

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Age-related mitochondrial dysfunction as a key factor in COVID-19 disease

Experimental Gerontology, Journal Year: 2020, Volume and Issue: 142, P. 111147 - 111147

Published: Nov. 7, 2020

Language: Английский

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Mitochondrial contributions to vascular endothelial dysfunction, arterial stiffness, and cardiovascular diseases

AJP Heart and Circulatory Physiology, Journal Year: 2021, Volume and Issue: 320(5), P. H2080 - H2100

Published: April 9, 2021

Cardiovascular disease (CVD) affects one in three adults and remains the leading cause of death America. Advancing age is a major risk factor for CVD. Recent plateaus CVD-related mortality rates high-income countries after decades decline highlight critical need to identify novel therapeutic targets strategies mitigate manage CVD development progression. Vascular dysfunction, characterized by endothelial dysfunction large elastic artery stiffening, independently associated with an increased incidence therefore attractive target prevention management. mitochondria have emerged as important player maintaining vascular homeostasis. As such, age- disease-related impairments mitochondrial function contribute consequent increases risk. This review outlines role discusses ramifications on health setting disease. The adverse consequences mitochondrial-derived reactive oxygen species, impaired quality control, defective calcium cycling are emphasized, particular. Current evidence both lifestyle pharmaceutical mitochondrial-targeted improve also presented.

Language: Английский

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Exosomes Derived from Adipose Mesenchymal Stem Cells Promote Diabetic Chronic Wound Healing through SIRT3/SOD2

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2568 - 2568

Published: Aug. 18, 2022

Chronic wounds resulting from diabetes are a major health concern in both industrialized and developing countries, representing one of the leading causes disability death. This study aimed to investigate effect adipose mesenchymal stem cell-derived exosomes (ADSC-exos) on diabetic mechanism underlying this effect. The results showed that ADSC-exos could improve oxidative stress secretion inflammatory cytokines wounds, thereby increasing periwound vascularization accelerating wound healing. At cellular level, reduced reactive oxygen species (ROS) generation human umbilical vein endothelial cells (HUVECs) improved mitochondrial function high-glucose environment. Moreover, Western blot analysis environment decreased Sirtuin 3 (SIRT3) expression, while exosome treatment increased SIRT3 expression. activity superoxide dismutase 2 (SOD2) was enhanced, level decreased. Further, interference experiments indicated effects angiogenesis were partly dependent SIRT3. After inhibited, ROS production increased, membrane potential SOD2 These findings confirmed high-glucose-induced stress, promote angiogenesis, reduce functional impairment response by regulating SIRT3/SOD2, thus promoting

Language: Английский

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Sirtuins in atherosclerosis: guardians of healthspan and therapeutic targets

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 19(10), P. 668 - 683

Published: March 30, 2022

Language: Английский

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Sirt3 ameliorates mitochondrial dysfunction and oxidative stress through regulating mitochondrial biogenesis and dynamics in cardiomyoblast.

Cellular Signalling, Journal Year: 2022, Volume and Issue: 94, P. 110309 - 110309

Published: March 16, 2022

Language: Английский

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