Scpep1 inhibition attenuates myocardial infarction-induced dysfunction by improving mitochondrial bioenergetics

doi:10.1093/eurheartj/ehaf032

科研成果详情

题名	Scpep1 inhibition attenuates myocardial infarction-induced dysfunction by improving mitochondrial bioenergetics
作者	Guilin Chen1,2; Jing Gan 2; Fan Wu 2; Zengxian Zhou1; Zikun Duan1,3; Ke Zhang1; Songxue Wang1; Hua Jin 1; Yulin Li 4; Chi Zhang 3; Zhuofeng Lin1,2,5
发表日期	2025-02-11
发表期刊	European heart journal 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Cardiomyocyte apoptosis Mitochondrial bioenergetics Myocardial infarction Pex3 Scpep1
摘要	Myocardial infarction (MI) is an ischaemic cardiovascular disease associated with increased morbidity and mortality. Previous studies have suggested that serine carboxypeptidase 1 (Scpep1) is involved in vascular diseases; however, its role in cardiac diseases remains unclear. This study aims to explore the role of Scpep1 in regulating cardiac homeostasis during MI., The impact of Scpep1 deficiency or cardiac-specific knock-down and Scpep1 overexpression on heart function was evaluated in mice with MI. Its downstream functional mediators of Scpep1 were elucidated using proteomic analysis and confirmed by employing loss- and gain-of-function strategies., Circulating and cardiac Scpep1 levels were up-regulated in mice with MI. Genetic ablation or cardiac-specific knock-down of Scpep1 alleviated MI-induced cardiac dysfunction and damage in mice. In contrast, cardiac-specific Scpep1 overexpression aggravated these adverse effects. Mechanistically, Scpep1 exacerbated MI-induced cardiac dysfunction and damage by impaired mitochondrial bioenergetics via binding to Pex3 to promote its degradation, ultimately contributing to mitochondrial fission and apoptosis. Moreover, the expressional profiles of Scpep1 in plasma samples and heart tissues of patients with MI or ischaemic cardiomyopathy were in line with those observed in the mouse models. In addition, pharmaceutical inhibition of Scpep1 notably improved MI-induced cardiac dysfunction and damage by improving mitochondrial fragmentation and bioenergetics post-MI., Scpep1 deficiency mitigates MI by improving Pex3-mediated mitochondrial fission and subsequent cardiomyocyte apoptosis. Scpep1 constitutes a potential therapeutic target for attenuating MI.
资助项目	National Key Research and Development Program of China;Natural Science Foundation of China
ISSN	0195-668X
EISSN	1522-9645
DOI	10.1093/eurheartj/ehaf032
收录类别	PUBMED
URL	查看原文
PubMed ID	39932164
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/225874
专题	药学院（分析测试中心）其他_附属第三医院（瑞安市人民医院）
作者单位	1.School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China.; 2.The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan 523326, China.; 3.Rui'an People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325207, China.; 4.Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Anzhen Hospital of Capital Medical University, Beijing 100029, China.; 5.The Innovation Center of Cardiometabolic Disease, Guangdong Medical University, Dongguan 523326, China.
第一作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Guilin Chen,Jing Gan,Fan Wu,et al. Scpep1 inhibition attenuates myocardial infarction-induced dysfunction by improving mitochondrial bioenergetics[J]. European heart journal,2025.
APA	Guilin Chen., Jing Gan., Fan Wu., Zengxian Zhou., Zikun Duan., ... & Zhuofeng Lin. (2025). Scpep1 inhibition attenuates myocardial infarction-induced dysfunction by improving mitochondrial bioenergetics. European heart journal.
MLA	Guilin Chen,et al."Scpep1 inhibition attenuates myocardial infarction-induced dysfunction by improving mitochondrial bioenergetics".European heart journal (2025).