Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome

• Published in: Journal of the American Heart Association 2019-08, Vol.8 (15), p.e012617-e012617
• Main Authors: Scrimgeour, Laura A, Potz, Brittany A, Aboul Gheit, Ahmad, Shi, Guangbin, Stanley, Melissa, Zhang, Zhiqi, Sodha, Neel R, Ahsan, Nagib, Abid, M Ruhul, Sellke, Frank W
• Format: Article
• Language: English
• Subjects: angiogenesis; Animals; cardiovascular disease; Chronic Disease; coronary vessels; Disease Models, Animal; extracellular vesicles; Extracellular Vesicles - physiology; Male; Metabolic Syndrome - complications; Myocardial Ischemia - complications; Myocardial Ischemia - therapy; Neovascularization, Physiologic; Original Research; Swine
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.119.012617

Background Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. Methods and Results Nineteen male Yorkshire pigs were given a high-fat diet for 4 weeks, then underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs received either intramyocardial vehicle (n=6), EVs (high-fat diet with myocardial EV injection [HVM]; n=8), or HVM and calpain inhibition (n=5). Five weeks later, myocardial function, perfusion, coronary vascular density, and cell signaling were examined. Perfusion in the collateral-dependent myocardium was increased during rapid ventricular pacing in the HVM group in both nonischemic (P=0.04) and ischemic areas of the ventricle (P=0.05). Cardiac output and stroke volume were significantly improved in the HVM group compared with the control group during ventricular pacing (P=0.006). Increased arteriolar density was seen in the HVM group in both nonischemic and ischemic myocardium (P=0.003 for both). However, no significant changes in the capillary density were observed between the control, HVM, and HVM and calpain inhibition groups (P=0.07). The group that received EVs with oral calpain inhibition had neither increased vessel density (P>0.99) nor improvement in blood flow or cardiac function (P=0.48) when compared with the control group. Conclusions These findings suggest that EVs promote angiogenesis in areas of chronic myocardial ischemia and improve cardiac function under conditions of diet-induced metabolic syndrome.