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Hydrogen Sulfide Ameliorates Heart Aging by Downregulating Matrix Metalloproteinase-9
Kaichuan He1, Huaxing Zhang2, Bo Tan3
1Department of Physiology, Hebei Medical University, 050017, Hebei, China.
Insights
Supplementing with hydrogen sulfide (H2S) combats age-related cardiac decline by reducing matrix metalloproteinase-9 (MMP-9) and improving heart function. This study shows H2S preserves cardiac structure and function during aging.
Area of Science:
- Cardiovascular Science
- Aging Research
- Biochemistry
Background:
- Aging is a major risk factor for cardiovascular diseases, characterized by increased matrix metalloproteinase-9 (MMP-9) and decreased hydrogen sulfide (H2S) in the heart.
- Age-related cardiac dysfunction includes impaired diastolic function, fibrosis, and structural changes.
Purpose of the Study:
- To investigate if exogenous H2S supplementation can counteract age-associated cardiac decline.
- To determine the effects of H2S on cardiac H2S levels, MMP-9 expression, and cardiac morphology and function in aging.
Main Methods:
- Analysis of plasma H2S and MMP-9 levels in relation to age in humans.
- Administration of sodium hydrosulfide (NaHS) to aged mice and assessment of cardiac function, structure, fibrosis, and molecular markers (MMP-9, CSE).
- In vitro studies using small interfering RNA to elucidate the relationship between MMP-9 and cystathionine gamma-lyase (CSE).
Main Results:
- Plasma H2S levels decrease, while MMP-9 levels increase with age in humans.
- Aging mice exhibited reduced cardiac H2S, impaired diastolic function, and increased cardiac fibrosis.
- H2S supplementation in aged mice improved cardiac function, structure, and reduced fibrosis and MMP-9 expression.
Conclusions:
- Hydrogen sulfide (H2S) plays a protective role in the aging heart.
- H2S maintains cardiac structure and function during aging, partly by inhibiting MMP-9 expression.
Purpose:
Aging contributes significantly to cardiovascular diseases and cardiac dysfunction, leading to the upregulation of matrix metalloproteinase-9 (MMP-9) in the heart and a significant decrease in hydrogen sulfide (H2S) content, coupled with impaired cardiac diastolic function. This study explores whether supplementing exogenous hydrogen sulfide during aging ameliorates the decline in H2S concentration in the heart, suppresses MMP-9 expression, and improves the age-associated impairment in cardiac morphology and function.
Methods:
We collected plasma from healthy individuals of different ages to determine the relationship between aging and H2S and MMP-9 levels through Elisa detection and liquid chromatography-tandem mass spectrometry (LC/MC) detection of plasma H2S content. Three-month-old mice were selected as the young group, while 18-month-old mice were selected as the old group, and sodium hydrosulfide (NaHS) was injected intraperitoneally from 15 months old until 18 months old as the old + NaHS group. Plasma MMP-9 content was detected using Elisa, plasma H2S content, cardiac H2S content, and cystathionine gamma-lyase (CSE) activity were detected using LC/MC, and cardiac function was detected using echocardiography. Heart structure was assessed using hematoxylin and eosin staining, Masone staining was used to detect the degree of cardiac fibrosis, while western blot was used to detect the expression of MMP-9, CSE, and aging marker proteins. Knockdown of MMP-9 and CSE in H9c2 cells using small interfering RNA was carried out to determine the upstream-downstream relationship between MMP-9 and CSE.
Results:
H2S content in the plasma of healthy individuals decreases with escalating age, whereas MMP-9 level rises with age progression. Aging leads to a decrease in H2S levels in the heart and plasma of mice, severe impairment of cardiac diastolic function, interstitial relaxation, and fibrosis of the heart. Supplementing with exogenous H2S can improve these phenomena.
Conclusion:
H2S maintains the structure and function of the heart by inhibiting the expression of MMP-9 during the aging process.
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