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

Research output: Contribution to journalArticle

Authors

  • Laura A. Scrimgeour
  • Brittany A. Potz
  • Ahmad Aboul Gheit
  • Guangbin Shi
  • Melissa Stanley
  • Zhiqi Zhang
  • Neel R. Sodha
  • Nagib Ahsan
  • M. Ruhul Abid
  • Frank W. Sellke

External Institution(s)

  • Brown University
  • Rhode Island Hospital

Details

Original languageEnglish (US)
Article numbere012617
JournalJournal of the American Heart Association
Volume8
Issue number15
StatusPublished - Aug 6 2019
Peer-reviewedYes

Abstract

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.

    Research areas

  • angiogenesis, cardiovascular disease, coronary vessels, extracellular vesicles

Citation formats

APA

Scrimgeour, L. A., Potz, B. A., Aboul Gheit, A., Shi, G., Stanley, M., Zhang, Z., ... Sellke, F. W. (2019). Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome. Journal of the American Heart Association, 8(15), [e012617]. https://doi.org/10.1161/JAHA.119.012617

Harvard

Scrimgeour, LA, Potz, BA, Aboul Gheit, A, Shi, G, Stanley, M, Zhang, Z, Sodha, NR, Ahsan, N, Abid, MR & Sellke, FW 2019, 'Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome', Journal of the American Heart Association, vol. 8, no. 15, e012617. https://doi.org/10.1161/JAHA.119.012617