AT2R gene transfer to rat carotid arteries inhibits neointimal hyperplasia after balloon angioplasty

AIM: To study the effects of angiotensin Ⅱ type 2 receptor (AT2R) gene transfer on neointimal hyperplasia in rat carotid arteries after balloon angioplasty. METHODS:AT2R gene was transfected into rat carotid arteries with pAdCMV/AT2R after the establishment of rat carotid balloon injury restenosis model. The arteries were harvested at 7 days, 14 days and 21 days after gene transfer. The expression of AT2R, AT1R, PCNA in arteries and morphology analysis were evaluated by RT-PCR, immunohistochemistry and HE staining. The expressions of AT2R and PCNA were measured by double immunofluorescence staining and confocal microscope. RESULTS:pAdCMV/AT2R delivered into injured rat carotid arteries significantly up-regulated the levels of AT2R mRNA and protein in neointima from day 7 to day 21, but the levels of AT1R was not significantly different (P>0.05). pAdCMV/AT2R transfection significantly decreased the expression of PCNA in neointima at day 14 ［(27.29±5.81)% vs ( 72.25±4.47)%, (68.43±9.12)%，P<0.01］. At day 21, compared with no transfection group and pAd-GFP transfection group, pAdCMV/AT2R transfection reduced I/M (intimal/medial area) ratio significantly (0.78±0.06 vs 1.44±0.22, 1.36±0.21， respectively, P<0.01). No significant difference between pAd-GFP group and no transfection group was observed. CONCLUSION: Gene transfer of AT2R from lumen may effectively inhibit VSMC proliferation and neointimal hyperplasia in the rat carotid arteries after balloon angioplasty. The cross-talk between AT1R and AT2R may operate via signaling pathway, but not via counteraction of receptor expression.