Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 27, Issue 2, Pages 317-324Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000254684.80662.44
Keywords
microcirculation (resistance arteries); remodeling; blood flow; shear stress; endothelium; nitric oxide; matrix metalloproteases
Categories
Ask authors/readers for more resources
Objective-Blood flow is altered in metabolic and ischemic diseases with dramatic consequences. Resistance arteries structure and function remodel in response to chronic blood flow changes through a mechanism remaining mainly unknown. We hypothesized that the NO pathway and matrix metalloproteases (MMPs) activation might play a role in flow (shear stress)-induced microvascular remodeling. Methods and Results-Mesenteric resistance arteries were ligated to alter blood flow in vivo for 4 or 14 days: arteries were submitted to high (HF), low (LF), or normal flow (NF). Rats were treated with L-NAME, the angiotensin converting enzyme inhibitor perindopril or the MMPs inhibitor doxycycline. After 14 days, outward hypertrophic remodeling occurred in HF arteries in association with eNOS overexpression. MMP9 activity increased in the early phase (day 4). HF-remodeling was prevented by L-NAME, eNOS gene knockout, and doxycycline. L-NAME prevented eNOS overexpression and MMPs activation whereas doxycycline only prevented MMPs activation. In LF arteries diameter reduction was associated with a decreased eNOS expression without change in MMPs expression and activation. LF-remodeling was reduced by perindopril. Conclusions-In resistance arteries, high flow induced diameter enlargement and wall hypertrophy associated with the sequential activation of eNOS and MMP9.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available