Scpep1 inhibition attenuates myocardial infarction-induced dysfunction by improving mitochondrial bioenergetics
Background and Aims
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.
Methods
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.
Results
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.
Conclusions
Scpep1 deficiency mitigates MI by improving Pex3-mediated mitochondrial fission and subsequent cardiomyocyte apoptosis. Scpep1 constitutes a potential therapeutic target for attenuating MI.
Top-30
Journals
|
1
2
|
|
|
European Heart Journal
2 publications, 25%
|
|
|
Journal of Nanobiotechnology
1 publication, 12.5%
|
|
|
Chinese Chemical Letters
1 publication, 12.5%
|
|
|
MedComm
1 publication, 12.5%
|
|
|
Journal of Agricultural and Food Chemistry
1 publication, 12.5%
|
|
|
ACS Nano Medicine
1 publication, 12.5%
|
|
|
Advanced Functional Materials
1 publication, 12.5%
|
|
|
1
2
|
Publishers
|
1
2
|
|
|
Oxford University Press
2 publications, 25%
|
|
|
Wiley
2 publications, 25%
|
|
|
American Chemical Society (ACS)
2 publications, 25%
|
|
|
Springer Nature
1 publication, 12.5%
|
|
|
Elsevier
1 publication, 12.5%
|
|
|
1
2
|
- We do not take into account publications without a DOI.
- Statistics recalculated weekly.