Intramyocardial injection of hypoxia-conditioned extracellular vesicles modulates apoptotic signaling in chronically ischemic myocardium.

Publication/Presentation Date

9-1-2023

Abstract

OBJECTIVE: Limited treatments exist for nonoperative chronic coronary artery disease. Previously, our laboratory has investigated extracellular vesicle (EV) therapy as a potential treatment for chronic coronary artery disease using a swine model and demonstrated improved cardiac function in swine treated with intramyocardial EV injection. Here, we seek to investigate the potential cardiac benefits of EVs by using hypoxia-conditioned EVs (HEV). Specifically, this study aims to investigate the effect of HEV on apoptosis in chronically ischemic myocardium in swine.

METHODS: Fourteen Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex artery. Two weeks later, swine underwent redo left thoracotomy with injection of either saline (control, n = 7) or HEVs (n = 7). After 5 weeks, swine were euthanized for tissue collection. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to quantify apoptosis. Immunoblotting was used for protein quantification.

RESULTS: Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed a decrease in apoptosis in the HEV group compared with the control (

CONCLUSIONS: In chronic myocardial ischemia, treatment with HEV results in a decrease in overall apoptosis, possibly through the activation of both pro-survival and anti-apoptotic signaling pathways.

Volume

15

First Page

220

Last Page

228

ISSN

2666-2736

Disciplines

Medicine and Health Sciences

PubMedID

37808040

Department(s)

Fellows and Residents, Department of Surgery, Department of Surgery Residents

Document Type

Article

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