AC-SDKP treatment protects heart against excessive myocardial injury and heart failure in mice
Peng H, Xu J, Yang XP, Kassem KM, Rhaleb IA, Peterson E, and Rhaleb NE. AC-SDKP treatment protects heart against excessive myocardial injury and heart failure in mice. Can J Physiol Pharmacol 2019; Epub ahead of print.
Canadian journal of physiology and pharmacology
Myocardial infarction (MI) in mice results in cardiac rupture at 4-7 days post-MI, whereas cardiac fibrosis and dysfunction occur later. Ac-SDKP has anti-inflammatory, anti-fibrotic, and pro-angiogenic properties. We hypothesized that Ac-SDKP reduces cardiac rupture and adverse cardiac remodeling, and improves function by promoting angiogenesis and inhibiting detrimental reactive fibrosis and inflammation after MI. C57BL/6J mice were subjected to MI and treated with Ac-SDKP (1.6 mg/kg/day) for 1 or 5 weeks. We analyzed: 1) intercellular adhesion molecule-1 (ICAM-1) expression; 2) inflammatory cell infiltration and angiogenesis; 3) gelatinolytic activity; 4) incidence of cardiac rupture; 5) p53, the endoplasmic reticulum (ER) stress marker CCAAT/enhancer binding protein homology protein (CHOP), and cardiomyocyte apoptosis; 6) sarcoplasmic reticulum Ca2+ ATPase (SERCA2) expression; 7) interstitial collagen fraction (ICF) and capillary density; and 8) cardiac remodeling and function. Acutely, Ac-SDKP reduced cardiac rupture, decreased ICAM1 expression and the number of infiltrating macrophages, decreased gelatinolytic activity, p53 expression, and myocyte apoptosis, but increased capillary density in the infarction border. Chronically, Ac-SDKP improved cardiac structures and function, reduced CHOP expression and ICF, and preserved myocardium SERCA2 expression. Thus, Ac-SDKP decreased cardiac rupture, ameliorated adverse cardiac remodeling, and improved cardiac function after MI, likely through preserved SERCA2 expression and inhibition of ER stress.
ePub ahead of print