Impaired angiogenesis in Diabetes: unravelling the role of Glyoxalase 1 and methylglyoxal (DSB.AD003.020)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOMI)

Project manager

CLAUDIA MIELE
Phone number: 0817463605
Email: c.miele@ieos.cnr.it

Abstract

Decreased availability of endothelium-derived nitric oxide (NO) accompanied by impaired endothelium-dependent vasorelaxation represent a common feature of endothelial dysfunction in diabetic individuals, and an important cause of vascular disease. The major morbidity and mortality associated with diabetes is due to the development of both macro- and micro-vascular complications. However, the mechanism(s) by which endothelial function becomes impaired in the vascular endothelium of diabetic subjects remains poorly understood. Generation of Advanced Glycation End-products (AGEs) has an important role in the development of hyperglycaemia-induced endothelial damage. Methylglyoxal (MG) is the most reactive AGE, detoxified by the glyoxalase-1 (Glo1). Several studies have shown that increased MG-derived AGE levels in diabetic patients are associated with vascular complications. This project aims at elucidating the effect of increased MG levels due to Glo1 knockdown on endothelial cell function, and on the development of vascular complications associated with diabetes both in vitro in endothelial cells (MAEC Glo1-/+) and in vivo in glyoxalase-1 deficient mice (Glo1-/+ mice).

Goals

The specific aims are:
1. To investigate the molecular mechanisms involved in the effect of MGO accumulation on
endothelial cell function and angiogenesis;
2. To assess glucose homeostasis, angiogenesis and vascular function in Glo1-/+ mice.
3. To evaluate MGO effects on neuronal function

Start date of activity

08/09/2015

Keywords

Type 2 diabetes, Glyoxalase 1, angiogenesis

Last update: 21/01/2025