The effects of mutation of PKA phosphorylation site of Mfn2 on the intimal proliferation after balloon injury of carotid artery in rats / 中华急诊医学杂志

ABSTRACT

Objective To study the effects of protein kinase A (PKA) phosphorylation site' s mutation of mitofusin-2 (Mfn2) on intimal proliferation after balloon injury of carotid artery of rats. Method Rat model of carotid artery balloon injury was established and infected with Adv-LacZ, Adv-Mfn2, AdvMfn2-S442A or Adv-Mfn2-S442D from the peri-arterial sheathes of vessels, while phosphate buffered solution (PBS) used instead of above infectious adenovirus as uninfected group and sham operation as control group. The rats were sacrificed 14 days after balloon injury of carotid artery in order to measure the level of Mfn2 protein and the prol9iferation cell nuclear antigen (PCNA) with immunohistochemistry staining. The morphology of vessels was observed with HE staining. All data were statistically analyzed with ANOVA and Dunnett-t test. Results Fourteen days after surgery, the levels of Mfn2 protein significantly increased in arteries infected with Adv-Mfn2, Adv-Mfn2-S4442A and Adv-Mfn2-S442D compared with those in control group, sham operation group and Adv-LacZ infected group. The ratio of intimal area/medial area (I/M) and percentage of PCNA positive cells in both Adv-Mfn2 and Adv-Mfn2-S442A groups markedly decreased compared with control group (P ＜0. 01 ) . Compared with the Adv-Mfn2 group, the I/M and the percentage of PCNA positive cells reduced more significantly in Adv-S442A group (P ＜ 0. 01 ) . However,the I/M and the percentage of PCNA positive cells in Adv-LacZ and Adv-S442D groups were not significantly different from those found in the control group. Conclusions The over-expression of Mfn2 gene may effectively inhibit intimal proliferation after balloon injury of carotid artery of rats. The inhibitory effects of Mfn2-S442A are more obvious than those of Mfn2. However, the Mfn2-S442D is out of the inhibitory effect on neo-intimal proliferation.