GLP-1 Promotes Angiogenesis in Human Endothelial Cells in a Dose-dependent Manner, Through the Akt, Src and PKC Pathways

Overview

Journal Metabolism

Specialty Endocrinology

Date 2013 May 21

PMID 23684008

Citations 30

Authors

Konstantinos N Aronis

John P Chamberland

Christos S Mantzoros

Affiliations

Soon will be listed here.

Abstract

Introduction: Novel anti-diabetic medications that mimic or augment the physiological actions of GLP-1 improve cardiovascular risk factors in diabetics and GLP-1 has been proposed to have a beneficial role in the cardiovascular system. GLP-1 may have a direct cardioprotective role by decreasing infarct size and protecting from ischemia-reperfusion injury while prolonging survival in rodent models. The mechanisms underlying these observations remain largely unknown. In vitro studies suggest that GLP-1 may promote endothelial cell proliferation, but no study to date has evaluated a potential direct effect of GLP-1 on angiogenesis.

Specific Aim: To evaluate whether GLP-1 affects angiogenesis in humans and to elucidate underlying molecular mechanisms.

Material And Methods: We utilized a 3D culture system where spherules of human umbilical vein endothelial cells (HUVECs) embedded in a collagen scaffold were treated with escalating doses of human recombinant GLP-1 (50-2000 nmol/L) and the formation of new vessels was observed and quantified. Signaling inhibitors were utilized to identify molecular pathways through which GLP-1 promotes angiogenesis.

Results: We demonstrate that GLP-1 promotes angiogenesis in a dose-dependent manner. The maximum effect on angiogenesis was observed at a GLP-1 dose of 500 nmol/L, while increased angiogenesis occurred in response to doses ranging from 200 nmol/L to 1000 nmol/L. Pre-treatment of the system with Akt inhibitor IV, Bisindolylmaleimide (PKC inhibitor) and src inhibitor I resulted in a significant decrease of the GLP-1 induced angiogenesis.

Conclusions: This is the first study to demonstrate that GLP-1 promotes angiogenesis in a HUVEC three dimensional in vitro model. This effect requires pharmacological doses and is mediated through the Akt, PKC and src pathways.

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