Angiotensin-converting enzyme 2 gene transfer attenuates neointimal formation after carotid artery ischemia-reperfusion injury in rats.
- Author:
Xu-wei WU
1
;
Zhuo-qiang LU
1
;
Jing-jing GONG
1
;
Hua-jun WANG
1
;
Chang-sheng XU
1
;
Xue-qing JIN
2
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Carotid Artery, Common; pathology; Gene Transfer Techniques; MAP Kinase Signaling System; Male; Muscle, Smooth, Vascular; pathology; Myocytes, Smooth Muscle; pathology; Neointima; pathology; Neovascularization, Pathologic; Peptidyl-Dipeptidase A; genetics; physiology; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; physiology; Reperfusion Injury; pathology
- From: Chinese Journal of Cardiology 2013;41(9):771-777
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effects of lentiviral recombinant angiotensin-converting enzyme 2 (LV-ACE2) gene transfer on the neointimal formation after carotid artery ischemia-reperfusion injury (IRI) and related mechanisms.
METHODSIRI was induced in SD rats through the carotid artery clipping and rats were divided into IRI, IRI+LV-GFP, IRI+LV-ACE2, IRI+ paclitaxel groups (n = 10 each). Sham operated rats serve as normal control. Four weeks later, neointimal formation was observed on HE stained carotid artery sections. The protein expression of ACE2, α-SM-actin, CD31, AT1R and P-ERK were detected by immunohistochemistry.
RESULTS(1) Carotid artery neointimal hyperplasia was readily shown in IRI group [I/M: 1.517 ± 0.151 (4 weeks later) vs. 0.011 ± 0.004 (Sham), P < 0.01], which was significantly reduced in IRI+LV-ACE2 (0.71 ± 0.17) and IRI+ paclitaxel (0.89 ± 0.21) groups. (2) The growth of vascular smooth muscle cells and neovascularization were also significantly inhibited in IRI+LV-ACE2 group and the expression of α-SM-actin (5 843 ± 839 vs. 12 648 ± 1 760, P < 0.01) and CD31 [(12.40 ± 4.01)/mm(2) vs. (96.20 ± 17.79)/mm(2), P < 0.01], AT1R (1 219 ± 175 vs. 4 861 ± 545, P < 0.01) and P-ERK1/2 phosphorylation (1 040 ± 215 vs. 2 938 ± 286, P < 0.01) in the neointimal of the injury arteries in IRI+LV-ACE2 group were significantly downregulated compared to IRI group.
CONCLUSIONThis data suggest that ACE2 gene overexpression is able to attenuate neointimal formation after ischemia-reperfusion injury possibly through downregulating AT1 receptor expression and signal pathway of ERK1/2 phosphorylation.
