O polimorfismo A1166C do receptor tipo 1 da angiotensina II no infarto agudo do miocárdio

Abstract

ObjectiveTo assess the association of the A1166C polymorphism of the angiotensin II type-1 receptor (AT1R) gene with acute myocardial infarction and also with the severity of coronary artery disease. (OR = 1.35; AC vs AA (OR = 1.03; and AA+AC vs AA (OR = 1.33;. None of the severity criteria showed a significant correlation with the genotypes. Methods Conclusion According to our results, no correlation exists between the A1166C polymorphism of the angiotensin II type-1 receptor (AT1R) gene and acute myocardial infarction or the severity of coronary artery disease. Key words A1166C polymorphism, angiotensin II, acute myocardial infarction, coronary artery diseaseThe renin-angiotensin system comprises a cascade of enzymatic reactions, which results in the production of angiotensin II from the angiotensinogen substrate. The physiological effects of angiotensin II are mediated by a final common pathway, through angiotensin II binding to specific receptors located on the cell membrane 1,2 . Two isoforms of endothelial receptors for angiotensin II are known so far: AT1 and AT2. Most of their physiological effects are mediated by the activation of AT1-subtype receptors. The receptors belong to the superfamily of the G-protein-coupled receptors, and, in the case of AT1 receptors (AT1R), coupling occurs via Gq proteins. Consequently, stimulation of AT1 receptors activates phospholipase C, increases the levels of diacylglycerol (DAG) and inosotol triphosphate (IP3), elevates the intracellular Ca +2 concentration, and activates several kinases, modulating cell functions 3,4 . Angiotensin II acts as a mitogen in vascular smooth muscle cells by activating several signaling pathways, such as that of phospholipase C, phospholipase A 2 , and phospholipase D, as well as by activating a large number of kinases, such as tyrosine kinases, mitogen-activated protein kinases (MAPKs), c-src kinase, Janus-associated tyrosine kinase, and receptors with tyrosine-kinase activity. Angiotensin II also stimulates transcription factors, such as the activating protein 1, signal transduction and transcription activators (STATs), and the nuclear factor kappa B (NFkB) 5,6 . Several studies have reported that the proliferative effects of angiotensin II are mediated by the activation of AT1 receptors 7 . More recently, a study including patients with myocardial infarction and high circulating levels of angiotensin II reported that the administration of AT1R antagonists had a significant pharmacotherapeutic implication 8 . Cloning of cDNA of the AT1 receptor provided the identification of a polymorphism in the nontranslated region 3' (A1166C), corresponding to an A→C transversion (adenine replaced by cytosine) in the position of the nucleotide 1166 of the mRNA sequence, resulting in 1 heterozygous (AC) and 2 homozygous (CC and AA) genotypes 9 . The homozygous CC genotype seems to be associated with a greater incidence of myocardial infarction 10 . Increasing evidence has shown the importance of the participation of the renin-angiotensin system in th...

Bioactive Natural Products against Systemic Arterial Hypertension: A Past 20-Year Systematic and Prospective Review

“…The effects of Ang II are mediated by two distinct types of receptors: AT 1 and AT 2 , and the greatest interaction of this peptide occurs via the AT 1 receptors, causing vasoconstrictor action, arrhythmogenic effect, cell proliferation, thrombosis, coagulation, inflammation, and hypertrophy of vascular smooth muscle [ 114 , 115 ]. This Ang II signaling pathway with AT 1 receptors is carried out by the activation of the G protein, with consequent activation of phospholipase C- β and formation of 1,4,5-triphosphate and diacylglycerol, which in turn increases the intracellular concentration of calcium leading to vasoconstriction [ 116 ]. In addition to these effects, it is known that q Ang II via AT 1 receptors stimulates aldosterone secretion by the zona glomerulosa of the adrenal cortex [ 117 ].…”

Análise combinada de fatores genéticos e ambientais na hipertensão essencial em um município da região Amazônica

“…Epidemiological studies have suggested that genetic variants, including those of the genes for angiotensinogen (AGT) 1 , renin (REN) 2 , angiotensin-converting enzyme (ACE) 3 , angiotensin II receptor type 1 (AGTR1) 4,5 , and aldosterone synthase (CYP11B2) 6 increase the risk for EH. However, the influence of polymorphic forms of these genes has shown conflicting results in different populations 7,8 .…”

Avaliação da pressão arterial e da excreção renal de sodio em animais espontaneamente hipertensos (SHR) submetidos a atividade fisica programada

“…Esse processo promove acoplamento com a proteína G que estimula a fosfolipase beta. Uma vez estimulada, ela induz a formação de trifosfato de inositol e DAG, liberando Ca 2+ citoplasmático ao passo que ativa PKC e adenil-ciclase (CONTRA et al, 2008;CARVALHO-FILHO et al, 2007;ARAÚJO et al, 2004). Após essa ligação, a angiotensina II estimula a musculatura vascular lisa através vias de sinalização, como a fosfolipase C, fosfolipase A2 e fosfolipase D. Além disso, participa da ação de inúmeras quinases, tais como tirosinaquinases, proteína quinase ativada por mitógenos (MAPKs).…”

“…Após essa ligação, a angiotensina II estimula a musculatura vascular lisa através vias de sinalização, como a fosfolipase C, fosfolipase A2 e fosfolipase D. Além disso, participa da ação de inúmeras quinases, tais como tirosinaquinases, proteína quinase ativada por mitógenos (MAPKs). A Ang II também aciona a proteína ativadora-1, ativadores de transdução e transcrição (ESTEBAN, et al, 2008;ARAÚJO et al, 2004). Os mecanismos intracelulares da ANG II são mostrados na Figura 5 (CARVALHO-FILHO et al, 2008).…”

“…Revisão da Literatura Há dois subtipos específicos de receptores da Ang II denominados receptores AT1 e AT2. Eles estão localizados na membrana celular e encontram-se, predominantemente, na supra-renal, na musculatura vascular lisa, rins, coração e no cérebro (CONTRA et al, 2008;CARVALHO-FILHO et al, 2007;ARAÚJO et al, 2004;RIBEIRO;FLORÊNCIO, 2000). ) diminuindo a produção de óxido nítrico, um potente vasodilatador.…”