Adenoviral VEGF-B186R127S Gene Transfer Induces Angiogenesis and Improves Perfusion in Ischemic Heart

Overview

Journal iScience

Publisher Cell Press

Date 2021 Dec 17

PMID 34917905

Citations 6

Authors

Henna Korpela

Olli-Pekka Hatinen

Tiina Nieminen

Rahul Mallick

Pyry Toivanen

Jonna Airaksinen

Kaisa Valli

Mikko Hakulinen

Pekka Poutiainen

Jussi Nurro

Seppo Yla-Herttuala

Affiliations

Soon will be listed here.

Abstract

Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects. VEGF-B constructs were studied using adenovirus (Ad)-mediated intramyocardial gene transfers into the normoxic and ischemic porcine heart (n = 51). It was found that the unprocessed isoform VEGF-B186R127S is as efficient angiogenic growth factor as the native VEGF-B186 in normoxic and ischemic heart. In addition, AdVEGF-B186R127S increased myocardial perfusion reserve by 22% in ischemic heart without any side effects. AdVEGF-B127 (VEGFR-1 and Nrp-1 ligand) and AdVEGF-B109 (VEGFR-1 ligand) did not induce angiogenesis. Thus, VEGF-B186 is angiogenic only before its proteolytic processing to VEGF-B127. Only the VEGF-B186 C-terminal fragment was associated with arrhythmias.

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