Hydrogen Sulfide Ameliorates Heart Aging by Downregulating Matrix Metalloproteinase-9.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2024-06-17 DOI:10.1007/s10557-024-07586-w

Kaichuan He, Huaxing Zhang, Bo Tan, Chengqing Song, Zihui Liang, Lixia Zhang, Danyang Tian, Lin Xiao, Hongmei Xue, Qi Guo, Xu Teng, Sheng Jin, Cuixia An, Yuming Wu

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Abstract

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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硫化氢通过下调基质金属蛋白酶-9改善心脏衰老

目的：衰老是心血管疾病和心脏功能障碍的重要诱因，会导致心脏中基质金属蛋白酶-9（MMP-9）上调、硫化氢（H2S）含量显著下降以及心脏舒张功能受损。本研究探讨了在衰老过程中补充外源性硫化氢是否能改善心脏中 H2S 浓度的下降，抑制 MMP-9 的表达，并改善与年龄相关的心脏形态和功能损伤：我们采集了不同年龄健康个体的血浆，通过 Elisa 检测和液相色谱-串联质谱（LC/MC）检测血浆中 H2S 的含量，以确定衰老与 H2S 和 MMP-9 水平之间的关系。选择 3 个月大的小鼠为年轻组，18 个月大的小鼠为年老组，从 15 个月大至 18 个月大的小鼠腹腔注射硫氢化钠（NaHS）为年老 + NaHS 组。用 Elisa 检测血浆 MMP-9 含量，用 LC/MC 检测血浆 H2S 含量、心脏 H2S 含量和胱硫醚γ-赖氨酸酶（CSE）活性，用超声心动图检测心脏功能。用苏木精和伊红染色法评估心脏结构，用 Masone 染色法检测心脏纤维化程度，用 Western 印迹法检测 MMP-9、CSE 和衰老标志蛋白的表达。利用小干扰 RNA 在 H9c2 细胞中敲除 MMP-9 和 CSE，以确定 MMP-9 和 CSE 之间的上下游关系：结果：健康人血浆中的H2S含量随着年龄的增长而降低，而MMP-9的含量则随着年龄的增长而升高。衰老会导致小鼠心脏和血浆中的 H2S 含量下降，严重损害心脏舒张功能、间质松弛和心脏纤维化。补充外源性 H2S 可以改善这些现象：结论：H2S 可在衰老过程中抑制 MMP-9 的表达，从而维持心脏的结构和功能。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.