SM22α Inhibits The Expression Of Migration Related Molecules In AngⅡ-induced Vascular Hypertrophy

Objective: Hypertension is the key event of vascular remodeling.Vascular smooth muscle cell (VSMC) proliferation and hypertrophy arepathological basis of vascular remodeling diseases, including hypertension andatherosclerosis. Smooth muscle22alpha (SM22α), an importantcytoskeletal-associated protein, is one of the VSMC differentiation markers.Recent studies have demonstrated that SM22α plays key roles in VSMCproliferation, inflammation and oxidative stress.The renin-angiotensin system (RAS) plays an essential role in regulatingthe physiological processes of the cardiovascular system. As the primaryeffector molecule of this system, angiotensin (Ang) Ⅱ has multiplepathophysiological effects on VSMC, including increase in arterial pressure,induction of VSMC hypertrophy and so on. To investigate the effect ofSM22α on vascular hypertrophy, the carotid arteries of rats with hypertensionwere infected with recombinant adenovirus containing wild-type and mutantof SM22α.Methods and Results:1Ang Ⅱ plays a vital role in modulating blood pressure.Systolic blood pressure (SBP) of the animals was measured before genetransfer and the implantation of osmotic pumps. The administration with AngⅡ resulted in increase in SBP, compared with the vehicle.2SM22α and S181A mutant inhibit the vascular hypertrophy.Immunohistochemistry of cross-sections of the carotid artery showed theexpression of exogenous gene GFP following recombinant adenovirusinfection. The medial thickness of the carotid arteries increased after Ang Ⅱ infusion for13days in rats treated with Ang Ⅱ plus GFP or S181D,respectively. However, the overexpression of wild type SM22α and S181Amutant significantly reduced the thickness of the media. These results suggestthat blockade of SM22α phosphorylation inhibits the vascular hypertrophy.3SM22α and S181A mutant inhibit the expression of MMP-2andMMP-9.Immunohistochemistry showed that the levels of MMP-2and MMP-9were higher in Ang Ⅱ plus GFP, compared with vehicle plus GFP. Moreover,overexpression of S181D also improved the expression of them (P<0.01).However, there was a significant decrease in MMP-2and MMP-9in the arterywall transfected with Ad-GFP-SM22α and Ad-GFP-S181A (P<0.05). Thesedata showed that SM22α and S181A mutant but not S181D inhibit theexpression of MMP-2and MMP-9.4SM22α and S181A mutant inhibit the expression of ICAM-1andVCAM-1The immunohistochemical staining showed that the expression ofICAM-1and VCAM-1increased in the vessel wall treated by Ang Ⅱ withinfection of Ad-GFP-S181D and Ad-GFP (P<0.01), while Ad-GFP-SM22α orS181A inhibited their expression induced by Ang Ⅱ (P<0.05).Conclusions:1The hypertension model is successfully established in rats.2The recombinant adenovirus of SM22α infects the carotid arteries invivo.3Overexpression of SM22α and S181A mutant inhibits vascularhypertrophy, associated with the suppression of the expression of MMP-2,MMP-9, ICAM-1and VCAM-1.