Key Role of the NO-Pathway and Matrix Metalloprotease-9 in High Blood Flow-Induced Remodeling of Rat Resistance Arteries

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 27 Số 2 - Trang 317-324 - 2007
Odile Dumont1,2,3, Laurent Loufrani1,2,4, Daniel Henrion5,1,2
1From the CNRS UMR 6214; INSERM UMR 771; University of Angers, France.
2INSERM UMR 771
3Odile Dumont From the CNRS UMR 6214
4Laurent Loufrani From the CNRS UMR 6214
5Daniel Henrion From the CNRS UMR 6214

Tóm tắt

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.

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Thông tin xuất bản

Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 27 Số 2

317-324

Thông tin tác giả