 |
|
|
|
|
Volume 1, Number 1, March 2000
Mechanical strain-induced human vascular matrix synthesis: The role of angiotensin II
Adrian G Stanley, Hash Patel, Abigail L Knight, Bryan Williams Introduction: Reduced vascular compliance in patients with hypertension results from an increase
in extra-cellular matrix (ECM) protein deposition in blood vessels. At least two key factors,
namely mechanical strain and neurohumoral mediators, for example Angiotensin II (Ang II), promote
fibrogenesis within vessel walls; however potential interactions between these have not been
clearly defined. This work examined the direct effect of mechanical strain on matrix mRNA expression
and protein synthesis by human vascular smooth muscle (VSM) cells and identified the importance
of renin-angiotensin system (RAS) activation in stretch-induced matrix production.
Methods: Human VSM cells were exposed either to a cyclical mechanical strain regimen or to Ang II
in the presence or absence of the Ang II receptor (AT1 R) antagonist losartan or its more potent metabolite
EXP3174. Analysis of matrix mRNA expression (Northerns) and protein synthesis (ELISA) and cellular
AT1-receptor protein expression (Westerns) were determined.
Results: Ang II increased both collagen α1 (92%, SEM +/- 20%) mRNA expression and fibronectin (21%
+/- 6%) protein synthesis in static VSM cells compared with unstimulated controls. The effect
of Ang II was attenuated by antagonism of the AT1-receptor (AT1 R). Similarly, mechanical strain
induced an increase in both collagen α1 (102% +/- 30%) mRNA expression and fibronectin (50% +/-21%)
protein synthesis. Surprisingly, in the absence of exogenous Ang II, AT1-receptor blockade attenuated
this stretch-induced increase in matrix synthesis. Mechanical strain also induced an increase
in total cellular AT1-receptor protein (30.7% +/- 3.5%) compared with static cells.
Conclusion: Both mechanical strain and Ang II increased matrix gene expression and protein synthesis
by human VSM cells. The effect of strain was attenuated by AT1-receptor antagonism. Our results
further suggest that mechanical strain may sensitise human VSM cells to the fibrogenic actions
of Ang II, perhaps via upregulation of the AT1-receptor. JRAAS 2000;1:32-35. View full PDF article (open in new window)
Email this article Right click on this DOI link and copy link to cite this article (What is a DOI link?)
|
|
