Inhibition of neointima by angiotensin-converting enzyme inhibitor in porcine coronary artery balloon-injury model.

Content Provider	Semantic Scholar
Author	Morishita, Ryuichi Moriguchi, Atsushi Aoki, Motokuni Sakonjo, Hiroshi Matsumoto, Koichi Nakamura, Toshikazu Higaki, Jitsuo Ogihara, Toshio
Copyright Year	2001
Abstract	Because hepatocyte growth factor (HGF) stimulates growth of endothelial cells exclusively without replication of vascular smooth muscle cells, we hypothesized that HGF may play a role in cardiovascular disease. In human vascular smooth muscle cells, angiotensin II suppressed local vascular HGF production in a dose-dependent manner. Using a rat balloon-injury carotid artery model, we demonstrated that blockade of angiotensin II inhibited neointimal formation, accompanied by a significant increase in local HGF production. However, the relation of vascular HGF to endothelial function was not clarified. Moreover, it is important to test the hypothesis in animal models that are more similar to human restenosis. Thus, in the present study, we used a porcine coronary artery balloon-injury model to study the role of angiotensin II in regulation of the local HGF system in vivo. Expression of HGF mRNA was significantly decreased in balloon-injured coronary arteries versus intact vessels. An angiotensin-converting enzyme (ACE) inhibitor (perindopril) significantly inhibited neointimal formation after balloon injury compared with vehicle (P:<0.05). In addition, vasodilator response of balloon-injured coronary arteries to bradykinin was restored by perindopril treatment, whereas no vasodilator response was observed in balloon-injured vessels treated with vehicle. Vasodilator response of balloon-injured arteries induced by perindopril was completely abolished by N:(w)-nitro-L-arginine methyl ester. Of particular interest, vascular HGF mRNA was significantly increased in balloon-injured vessels treated with perindopril as compared with vehicle. Overall, the present study demonstrated that ACE inhibitor significantly inhibited neointimal formation, accompanied by significant improvement of endothelial dysfunction and a significant increase in local vascular HGF mRNA in vivo in a porcine coronary artery balloon-injury model. Given the strong mitogenic activity of HGF on endothelial cells, improvement of endothelial dysfunction by perindopril might be due to increased local HGF expression through enhancement of reendothelialization after balloon injury, in addition to its direct effect, ACE inhibition. Downregulation of the local vascular HGF system may play an important role in the pathogenesis of cardiovascular disease.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://hyper.ahajournals.org/content/hypertensionaha/37/2/270.full.pdf?download=true
PubMed reference number	11230284v1
Volume Number	37
Issue Number	2
Journal	Hypertension
Language	English
Access Restriction	Open
Subject Keyword	Angioplasty, Balloon, Coronary Angiotensin II Angiotensin-Converting Enzyme Inhibitors Angiotensins Animal Model Arginine Blood Vessel Bradykinin Cardiovascular Diseases Carotid Arteries Clarify Coronary artery Endothelial Cells Esters Hepatocyte Growth Factor Interleukin-6 Muscle Cells Muscle, Smooth, Vascular Myocytes, Smooth Muscle NG-Nitroarginine Methyl Ester Neointima Perindopril Porcine species Smooth muscle (tissue) Vasodilator Agents restenosis
Content Type	Text
Resource Type	Article