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Functional relevance of genetic variations of endothelial nitric oxide synthase and vascular endothelial growth factor in diabetic coronary microvessel dysfunction
Author(s) -
Joshi Mandar S,
Berger Philip J,
Kaye David M,
Pearson James T,
Bauer John A,
Ritchie Rebecca H
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12070
Subject(s) - medicine , diabetes mellitus , microvessel , vascular endothelial growth factor , endothelial dysfunction , angiogenesis , nitric oxide , neovascularization , pathogenesis , nitric oxide synthase , vascular endothelial growth factor a , endocrinology , bioinformatics , cardiology , vegf receptors , biology
Summary The prevalence of type 1 diabetes (T1D) is increasing worldwide and is associated with significant microvessel complications, of which nephropathy, retinopathy and neuropathy are the most commonly studied. Although clinically evident microvascular complications of diabetes are rarely seen in childhood, early vascular abnormalities develop during childhood and accelerate during puberty. Vascular endothelial growth factor ( VEGF ) is a major mediator of angiogenesis, which is regulated by endothelial nitric oxide synthase ( NOS 3) at several levels. Together, VEGF and NOS 3 play an important role in the pathogenesis of the microvascular complications of diabetes. Genetic variations in NOS 3 and VEGF critically regulate endothelial survival and function and increase the susceptibility of patients to develop severe microvessel complications. Identification of the risk factors for and improved understanding of the subclinical signs of these diabetic microvascular complications will enable implementation of therapeutic strategies, potentially changing the course of vascular complications and improving the prognosis of children, adolescents and young adults with diabetes. Moreover, early detection of these variations may have a prognostic value or may suggest interventional approaches to regulate these proteins in patients with diabetes.