IQGAP1 promotes the phenotypic switch of vascular smooth muscle by myocardin pathway: a potential target for varicose vein.
Recently, the architectural remodeling of venous vessel wall ranks as the basis of varicose veins development based on the phenotypic state of vascular smooth muscle cells (VSMCs). In this study, we firstly demonstrated an obvious up-regulation of IQ-domain GTPase-activating protein 1 (IQGAP1) in patients with varicose veins. Importantly, following stimulation with PDGF-BB for 4 h, a common inducer of phenotypic switch in VSMCs, a dramatically time-dependent increase in IQGAP1 expression was observed in human venous smooth muscle cells (HUVSMCs), concomitant with the down-regulation of SMC markers [including α-smooth muscle actin (SMA), smooth muscle calponin (CNN), SM22α (SM22)], suggesting a critical function of IQGAP1 during the switch of synthetic VSMC phenotype. Further analysis ascertained that IQGAP1 overexpression significantly inhibited the expression of SMA, SM and CNN, while its silencing dramatically promoted their expression levels. Moreover, the elevated IQGAP1 enhanced cell proliferation, migration and rearrangement. Mechanism assay confirmed that IQGAP1 overexpression notably blocked myocardin levels. Importantly, after transfection with myocardin siRNA, IQGAP1 down-regulation-induced decrease in cell proliferation, migration and cell rearrangement was remarkably attenuated. Together, these results demonstrated that IQGAP1 may regulate the phenotypic switch of VSMCs by myocardin pathway, which is critical for the pathological progression of varicose vein. Therefore, this study supports a prominent insight into how IQGAP1 possesses its benefit function in varicose veins development by regulating vascular remodeling.
Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu 215002, P. R. China.
Xianchen
X
Huang
Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu 215002, P. R. China.
Yiqi
Y
Jin
Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu 215002, P. R. China.
Dayong
D
Zhou
Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu 215002, P. R. China.
Guoxiong
G
Xu
Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu 215002, P. R. China.
Jian
J
Huang
Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Suzhou, Jiangsu 215002, P. R. China.
Liming
L
Shen
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014648:Varicose Veins / Q000378:metabolism* / Q000473:pathology; D066253:Vascular Remodeling; D014680:Veins / Q000378:metabolism / Q000473:pathology; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D000096985:Calponins; D000099251:Myocardin
D000199:Actins; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D020703:ras GTPase-Activating Proteins; D000096985:Calponins; D000099251:Myocardin; C541116:ACTA2 protein, human; C101203:IQ motif containing GTPase activating protein 1; C051615:transgelin
IQGAP1; VSMC; Varicose vein; vascular remodeling