RESUMO
Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase and marker of endothelial dysfunction, but the question remains as to whether asymmetric dimethylarginine is a marker of cardiovascular episodes or their independent risk factor. ADMA/DDAH (dimethylaminohydrolase) pathway regulates vascular endothelial growth factor (VEGF)-mediated angiogenesis due to its impact on the NO formation. The aim of the study was to assess the concentrations of asymmetric dimethylarginine and the angiogenic potential in the blood of subjects with type 2 diabetes (T2DM, n = 33) and patients with prediabetes (n = 32)-impaired fasting glycemia and/or impaired glucose tolerance (WHO criteria). The study found that both the prediabetes group and subjects with T2DM had significantly elevated concentrations of asymmetric dimethylarginine, significantly high levels of VEGF-A, low ratio of sVEGF-R1/VEGF-A, and sVEGF-R2/VEGF-A. This may suggest endothelial damage at early stages of carbohydrate metabolism dysfunction-before T2DM is diagnosed. Higher proangiogenic potential in prediabetes and T2DM patients than in healthy subjects, is not only the effect of an increase in VEGF-A levels, but also reduced inhibition of circulating receptors.
Assuntos
Arginina/análogos & derivados , Diabetes Mellitus Tipo 2/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Estado Pré-Diabético/fisiopatologia , Adulto , Idoso , Arginina/farmacologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Solubilidade , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Competitive inhibition of endothelial nitric oxide synthase (eNOS) is the main biological effect of asymmetric dimethylarginine (ADMA), i.e. the methylated derivative of L-arginine. The resulting low level of NO is becoming one of the elements of pathogenesis of numerous cardiovascular disorders, mainly related to atherosclerosis, but also other metabolic diseases including type 2 diabetes. It appears that a high level of ADMA is not only a marker of pathological conditions such as chronic kidney failure, but also a significant factor which damages the endothelium. Despite multiple studies, the mechanisms of reducing the level of ADMA, which would allow to inhibit the progression of cardiovascular diseases and effective treatment, e.g. by means of L-arginine supplementation or medicines which are lowering ADMA levels, are still unclear. Perhaps, linking ADMA with the processes of new blood cell formation (angiogenesis) will allow us to explain these multifactor mechanisms.
