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|Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension|
|Authors: ||Roncal, C. (Carmen)|
Orbe, J. (Josune)
Rodriguez, J.A. (José Antonio)
Belzunce, M. (M.)
Beloqui, O. (Óscar)
Diez, J. (Javier)
|Issue Date: ||2004|
|Publisher: ||Oxford University Press (OUP)|
|Publisher version: ||http://dx.doi.org/10.1016/j.cardiores.2004.03.023|
|Citation: ||Roncal C, Orbe J, Rodriguez JA, Belzunce M, Beloqui O, Diez J, et al. Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension. Cardiovasc Res 2004 Jul 1;63(1):176-185.|
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 (p<0.05). Laser confocal microscopy and Western blot analysis showed increased PAI-1 protein within ECM in Ang II-stimulated cultures. PAI-1 expression and protein secretion induced by Ang II in 4G/4G HUVEC was completely inhibited by preincubation with 0.05 microM losartan (p<0.01), indicating an AT1-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 (p<0.05).
CONCLUSIONS: 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.
|Permanent link: ||http://hdl.handle.net/10171/19656|
|Appears in Collections:||DA - CIMA - Cardiovasculares - Aterosclerosis e inflamación - Artículos de revista|
DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista
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