Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension
Open Access
- 1 July 2004
- journal article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 63 (1) , 176-185
- https://doi.org/10.1016/j.cardiores.2004.03.023
Abstract
Background: We examined the influence of the 4G/5G PAI-1 (plasminogen activator inhibitor) genotype on Angiotensin II (Ang II)-induced PAI-1 expression by human endothelial cells (HUVEC) in the presence and absence of AT1-receptor blocker losartan, and screened for this polymorphism in relation to plasma PAI-1 and arterial pressure in apparently healthy subjects. Methods and results: Genotyped cultured HUVEC were incubated with Ang II (10−8 M) with or without losartan up to 24 h. PAI-1 mRNA was determined in cell extracts and protein and activity assessed in supernatants and extracellular matrix (ECM). Ang II increased PAI-1 mRNA and activity in a genotype-dependent manner, higher values observed for 4G/4G HUVEC compared with 4G/5G and 5G/5G genotypes (pp1-mediated effect. In a group of hypertensives homozygous for the 4G allele, PAI-1 antigen was significantly increased (51.0±10.1 ng/ml) compared with normotensives (28.3±4.0 ng/ml) and hypertensives carrying the 5G allele (pConclusions: The 4G/5G PAI-1 polymorphism determines the endothelial PAI-1 upregulation by Ang II and the inhibitory response to losartan. Analysis of PAI-1 genotypes may help identifying subgroups of hypertensives at higher cardiovascular risk.Keywords
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