Corin Overexpression Reduces Myocardial Infarct Size and Modulates Cardiomyocyte Apoptotic Cell Death

Autor: Ryan D. Sullivan, Aiilyan K. Houng, Inna P. Gladysheva, Tai-Hwang M. Fan, Ranjana Tripathi, Guy L. Reed, Dong Wang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 10, p 3456 (2020)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms21103456
Popis: Altered expression of corin, a cardiac transmembrane serine protease, has been linked to dilated and ischemic cardiomyopathy. However, the potential role of corin in myocardial infarction (MI) is lacking. This study examined the outcomes of MI in wild-type vs. cardiac-specific overexpressed corin transgenic (Corin-Tg) mice during pre-MI, early phase (3, 24, 72 h), and late phase (1, 4 weeks) post-MI. Corin overexpression significantly reduced cardiac cell apoptosis (p < 0.001), infarct size (p < 0.001), and inhibited cleavage of procaspases 3, 9, and 8 (p < 0.05 to p < 0.01), as well as altered the expression of Bcl2 family proteins, Bcl-xl, Bcl2 and Bak (p < 0.05 to p < 0.001) at 24 h post-MI. Overexpressed cardiac corin also significantly modulated heart function (ejection fraction, p < 0.0001), lung congestion (lung weight to body weight ratio, p < 0.0001), and systemic extracellular water (edema, p < 0.05) during late phase post-MI. Overall, cardiac corin overexpression significantly reduced apoptosis, infarct size, and modulated cardiac expression of key members of the apoptotic pathway in early phase post-MI; and led to significant improvement in heart function and reduced congestion in late phase post-MI. These findings suggest that corin may be a useful target to protect the heart from ischemic injury and subsequent post-infarction remodeling.
Databáze: Directory of Open Access Journals
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