Biomarcadores de função endotelial em doenças cardiovasculares: hipertensão

Abstract

Abstract: The incidence of systemic arterial hypertension is increasing worldwide. The foundation of prevention is identification of people with hypertension. Nowadays, biomarkers are used to diagnose and stratify diseases and estimates prognosis. The objective of this study was to review articles published over the last 5 years on the subject of biomarkers of cardiovascular diseases. The PubMed, SciELO, Science Direct and MEDLINE databases were searched using the keywords: arterial hypertension, cardiovascular biomarkers, nitric oxide, endothelial function and asymmetric dimethylarginine. The studies reviewed show that cardiovascular diseases have complex etiologies. This article describes evidence demonstrating interactions between nitric oxide and asymmetric dimethylarginine that are involved in regulation, in metabolism, and in determination of intracellular levels, and also discusses other biomarkers related to hypertension. Some studies indicate that biomarkers are useful tools for prediction of cardiac events, whereas others state that they have little to contribute to assessments. Careful selection of tests and combinations of tests may be the key to validating use of biomarkers, in view of their low specificity for diagnosing hypertension.

Figura 1. Sinalização endotelial e mecanismo de relaxamento ou contração do músculo liso. eNOS: enzima óxido nítrico sintase endotelial; NO: óxido nítrico; GC: guanilato-ciclase; cGMP: guanosina monofosfato cíclico; Ca²⁺: íons de cálcio; ECE: enzima de conversão da endotelina; ET-1: endotelina 1; ETA, ETB: receptores das endotelinas – ETA e ETB em células de músculo liso vascular; O₂: radicais livres; ROS: espécies reativas de oxigênio; ADMA: dimetilarginina assimétrica; DDAH: dimetilarginina-dimetilamino-hidrolase.

Figura 2. Via da ADMA e sua relação com o NO. ADMA: dimetilarginina assimétrica; SAM: sadenosilmetionina; SAH: S-adenosil; PRMT1: enzima metiltransferase tipo 1; SDMA: dimetilarginina simétrica; L-NMMA: NG-monometil-L-arginina; RAS: sistema renina-angiotensina; ROS: espécies reativas de oxigênio; eNOS: enzima óxido nítrico sintase endotelial; NO: síntese de óxido nítrico.

Figure 1. Endothelial signaling and mechanism of relaxation or contraction of smooth muscle. eNOS: endothelial nitric oxide synthase enzyme; NO: nitric oxide; GC: guanylate cyclase; cGMP: cyclic guanosine monophosphate; Ca²⁺: calcium ions; ECE: endothelin conversion enzyme; ET-1: endothelin 1; ETA, ETB: receptors for endothelins – ETA and ETB in vascular smooth muscle cells; O₂: free radicals; ROS: reactive oxygen species; ADMA: asymmetric dimethylarginine; DDAH: dimethylarginine dimethylaminohydrolase.

Figure 2. ADMA pathway and its relationship with NO. ADMA: asymmetric dimethylarginine; SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine hydrolase; PRMT1: enzyme methyltransferase type 1; SDMA: symmetrical dimethylarginine; L-NMMA: NG-monomethyl-L-arginine; RAS: renin-angiotensin system; ROS: reactive oxygen species; eNOS: endothelial nitric oxide synthase enzyme; NO: nitric oxide synthesis.