Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical data suggest a link between the activation of the renin-angiotensin system and cardiovascular ischemic events. Leukocyte accumulation in the vessel wall is a hallmark of early atherosclerosis and plaque progression. E-Selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are adhesion molecules participating in mediating interactions between leukocytes and endothelial cells and have been found to be expressed in athero-sclerotic plaques. We investigated whether angiotensin II, the effector of the renin-angiotensin system, influences the endothelial expression of E-selectin, VCAM-1, and ICAM-1. In coronary endothelial cells derived from explanted human hearts, angiotensin II (10(-11) to 10(-5) mol/L) induced a concentration-dependent increase in E-selectin expression. The effect was measured by cell ELISA and duplex reverse-transcription polymerase chain reaction (RT-PCR) and reached its maximum at 10(-7) mol/L. Angiotensin II induced only a small increase in E-selectin expression in cardiac microvascular endothelial cells. VCAM-1 and ICAM-1 were not affected by angiotensin II stimulation. In addition, the effect of angiotensin II-induced E-selectin expression on leukocyte adhesion was quantified under flow conditions. Angiotensin II (10(-7) mol/L) increased leukocyte adhesion significantly to 67% of the maximal effect by tumor necrosis factor-alpha at a wall shear stress of 2 dyne/cm2. This adhesion was found to be E-selectin dependent, as demonstrated by blocking antibodies. The AT1-receptor antagonist DUP 753 significantly reduced E-selectin-dependent adhesion, whereas the AT2-receptor antagonist PD 123177 had no inhibitory effect. In addition, only AT1-receptor, but not AT2-receptor, mRNA could be detected by RT-PCR in coronary endothelial cells. Therefore, it is suggested that AT1 receptors mediate the effects of angiotensin II on E-selectin expression and leukocyte adhesion on coronary endothelial cells.
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PMID:Angiotensin II-induced leukocyte adhesion on human coronary endothelial cells is mediated by E-selectin. 935 54

The role of genetic susceptibility to coronary artery disease (CAD) seems to be quite important in young patients. In the last years the attention has been focused on polymorphisms influencing some biological functions (coagulation and fibrinolysis, platelets, vascular function, lipid metabolism, inflammation). The study of prothrombotic polymorphisms has kindled a deep interest. The role of atherosclerosis and thrombosis is different in the different ages. In all the studies we examined, the polymorphism G20210A in the prothrombin gene was associated with an increased risk of acute myocardial infarction (AMI) in young people, especially when other risk factors were present. Contradictory results have been found in the studies on Factor V Leiden: according to many authors the activated protein C resistance (APCR) is associated with an increased risk of AMI only in smokers, above all if women. On the other hand, some polymorphisms of the Factor VII gene seem to be protective. Young AMI could be also caused by a reduction of the fibrinolytic activity, as it was found when the allele 4G in the promoter of plasminogen activator inhibitor (PAI) gene is present. The attention has also been focused on the effects of variations in genes that influence platelet functions. According to a metanalysis of studies published up to 1999, there is no association between the polymorphism PlA1/A2 of the GP IIIa gene and young AMI, whereas there is doubt about the role of the polymorphism in the GP IIb e GP Ib genes. Moreover, it seems to be present an association with the polymorphisms in the thrombopoietin gene (C4830A and A5713G). Also the role of some genes coding for proteins influencing the vascular functions has been valued. Few studies were performed on genetics of the renin-angiotensin-aldosterone system and the results are insufficient and contradictory, such as those about the association between the polymorphism G894T in the eNOS gene or the polymorphism C677T in the MTHFR gene and young AMI. Genes coding for proteins involved in the lipid metabolism have been closely examined. Many polymorphisms were discovered in the Apo B gene: the variant C-516T was found to be associated with increased LDL levels, whereas the results about the association between this and other polymorphisms in the same gene (I/D of LAL sequence, PvuII, MspI, Asp4311Ser) and young AMI are discordant. On the other hand, the variant e4 of the ApoE gene was associated with an increased risk of AMI at young age in many works. In the last years, a particular interest has kindled the study of the relationship between inflammation, atherosclerosis and CAD. Even if the studies performed are few, it was found an association between young AMI and polymorphism C-260T in the CD14 gene, between coronarics atherosclerosis and polymorphism A516C in the E Selectin gene or polymorphisms Leu125Val and Ser563Asn in the PECAM1 gene.
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PMID:Genetic risk factors in myocardial infarction at young age. 1528 79