H2S protects from oxidative stress-driven ACE2 expression and cardiac aging.
Kalem Barrow1,2, Yuehong Wang1,2, Ruihuan Yu1,2
1School of Natural Sciences, Laurentian University, Sudbury, Canada.
Molecular and Cellular Biochemistry
|February 11, 2022
Summary
Hydrogen sulfide (H2S) helps maintain cardiac ACE2 levels, protecting against aging and oxidative stress. Targeting the cystathionine gamma-lyase (CSE)/H2S system may prevent heart disorders.
Area of Science:
- Cardiovascular Biology
- Metabolic Disorders
- Aging Research
Background:
- Cystathionine gamma-lyase (CSE)-derived hydrogen sulfide (H2S) is crucial for cardiac function.
- Angiotensin-converting enzyme 2 (ACE2) regulates the renin-angiotensin system, offering cardioprotection.
- The interplay between CSE/H2S and ACE2 in cardiac aging remains largely unexplored.
Purpose of the Study:
- To investigate the regulatory role of H2S on ACE2 expression in mouse hearts and rat cardiomyocytes under various stress conditions.
- To elucidate the impact of CSE deficiency and oxidative stress on cardiac ACE2 levels and cellular senescence.
- To explore the potential of targeting the CSE/H2S system for managing age-related and diabetes-associated heart conditions.
Main Methods:
- Assessed ACE2 protein levels in young and old mouse hearts, including CSE knockout (CSE KO) models.
- Utilized rat cardiomyocytes (H9C2 cells) exposed to hydrogen peroxide (H2O2) or lipid overload to induce oxidative stress and senescence.
- Administered sodium hydrosulfide (NaHS) as an H2S donor and manipulated ACE2 expression to evaluate protective effects.
Main Results:
- ACE2 protein levels decreased in aged mouse hearts and were further reduced in CSE KO mice, accompanied by increased oxidative stress.
- H2S supplementation reversed H2O2-induced suppression of ACE2 and attenuated cellular senescence in cardiomyocytes.
- High-fat diet and lipid overload increased ACE2 expression and oxidative stress in CSE KO hearts and cardiomyocytes, effects mitigated by exogenous H2S.
- ACE2 manipulation partially abrogated the protective effects of H2S against cellular senescence.
Conclusions:
- H2S dynamically regulates ACE2 levels, particularly under oxidative stress, playing a protective role in cardiac aging.
- The CSE/H2S pathway is a potential therapeutic target for mitigating cardiac dysfunction associated with aging and metabolic disorders like diabetes.
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