丝氨酸蛋白酶
心肌梗塞
心脏病学
心室重构
医学
内科学
蛋白酶抑制剂(药理学)
丝氨酸
药理学
化学
蛋白酶
酶
生物化学
免疫学
人类免疫缺陷病毒(HIV)
抗逆转录病毒疗法
病毒载量
作者
Qihao Sun,Wei Chen,Rimao Wu,Bo Tao,Ping Wang,Baiming Sun,Juan F Alvarez,Feiyang Ma,David Ceja Galindo,Sean P. Maroney,Anthony J. Saviola,Kirk C. Hansen,Shen Li,Arjun Deb
出处
期刊:Cardiovascular Research
[Oxford University Press]
日期:2024-04-26
被引量:1
摘要
Abstract Following myocardial infarction, the heart repairs itself via a fibrotic repair response. The degree of fibrosis is determined by the balance between deposition of extracellular matrix by activated fibroblasts and breakdown of nascent scar tissue by proteases that are secreted predominantly by inflammatory cells. Excessive proteolytic activity and matrix turnover has been observed in human heart failure and protease inhibitors in the injured heart regulate matrix breakdown. Serine protease inhibitors (Serpins) represent the largest and the most functionally diverse family of evolutionary conserved protease inhibitors and levels of the specific Serpin, SerpinA3, have been strongly associated with clinical outcomes in human myocardial infarction as well as non-ischemic cardiomyopathies. Yet, the role of Serpins in regulating cardiac remodeling is poorly understood. We observed the robust expression of Serpins in the infarcted murine heart and demonstrate that genetic deletion of SerpinA3n (mouse homolog of SerpinA3) leads to increased activity of substrate proteases, poorly compacted matrix and significantly worse post infarct cardiac function. Single cell transcriptomics complemented with histology in SerpinA3n deficient animals, demonstrated increased inflammation, adverse myocyte hypertrophy and expression of pro-hypertrophic genes. Proteomic analysis of scar tissue demonstrated decreased cross linking of extracellular matrix peptides consistent with increased proteolysis in SerpinA3n deficient animals. Taken together these observations demonstrate a hitherto unappreciated causal role of Serpins in regulating matrix function and post infarct cardiac remodeling.
科研通智能强力驱动
Strongly Powered by AbleSci AI