Hypertension is associated with the structural remodeling and stiffening of arteries and is known to increase cardiovascular risk. In the present study, we investigated the effects of overexpression and knock down of
profilin-1 on the vascular structural remodeling in spontaneous hypertensive rats (SHRs) using an adenovirus injection to knock down or overexpress
profilin-1 mRNA. As a control, blank adenovirus was injected into age-matched SHRs and Wistar-Kyoto rats (WKYs). We quantified arterial structural remodeling through morphological methods, with thoracic aortas stained with
hematoxylin-
eosin and picosirius red. Western blotting was performed to measure the
protein expression of
inducible nitric oxide synthase (iNOS) and
p38 mitogen-activated protein kinase (p38), and
peroxynitrite was quantified by immunohistochemical staining. Overexpression of
profilin-1 significantly promoted aortic remodeling, including an increase in vessel size, wall thickness, and
collagen content, whereas the knockdown of
profilin-1 could reverse these effects. In addition, the expression of phosphorylated p38, iNOS and
peroxynitrite was significantly upregulated in SHRs with
profilin-1 overexpression along with an increased level of
interleukin- 6 (IL-6). These changes could be reversed by knockdown of
profilin-1. Our results demonstrate a crucial role for
profilin-1 in
hypertension-induced arterial structural remodeling at least in part through the p38-iNOS-peroxynitrite pathway.