CaMKII-delta isoform regulation of neointima formation after vascular injury.
OBJECTIVE
The purpose of this study was to test the function of the calcium/calmodulin-dependent protein kinase II delta2 isoform (CaMKIIdelta2) in regulating vascular smooth muscle (VSM) cell proliferation and migration in response to vascular injury.


RESULTS
CaMKII isoform content was assessed in rat carotid arteries after balloon angioplasty-induced injury by Western blotting with isoform specific antibodies. Within 3 days after injury, a significant increase in CaMKIIdelta2 and decrease in CaMKIIgamma isoform content was observed in both medial smooth muscle and adventitial fibroblasts. Neointimal VSM cells expressed primarily the delta2 isoform. Incubation of the injured vessel with adenovirus encoding siRNA targeting CaMKIIdelta isoforms prevented upregulation of the delta2 isoform in the media and adventitia; inhibited cell proliferation assessed by PCNA expression in both layers and markedly inhibited neointima formation and adventitial thickening.


CONCLUSIONS
CaMKIIdelta2 is specifically induced in VSM and adventitial fibroblasts during the response of an artery to injury and is a positive regulator of proliferation and migration in the vessel wall contributing to neointima formation and vascular remodeling. This provides a potential mechanism for Ca2+-dependent regulation of VSM and myofibroblast proliferation and migration in response to vascular injury or disease.
House
Suzanne J
SJ
Center for Cardiovascular Sciences (MC8), Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208-3479, USA.
Singer
Harold A
HA
D000256:Adenoviridae; D000800:Angioplasty, Balloon; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D020212:Carotid Artery Injuries / Q000201:enzymology* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation
D015415:Biomarkers; D007527:Isoenzymes; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2