Impact of nifedipine on vascular smooth muscle cell differentiation. Implications for atherogenesis.
Although vascular smooth muscle cells (SMCs) play a key role in the development of atherosclerotic lesions, they are not a homogeneous cell type. Myosin has been used as a marker of SMC differentiation in order to identify distinct SMC populations in the adult rabbit aorta. The medial layer of the normal adult aorta contains predominantly 'adult' type SMCs, which express smooth muscle (SM) myosin isoforms exclusively, and a minority of 'immature' type SMCs, which coexpress SM and nonmuscle (NM) myosin isoforms. The size of this latter SMC subpopulation, showing the 'immature' pattern of myosin isoform expression, increases markedly in the aortic media during experimental atherogenesis, and represents a major SMC type in the atherosclerotic plaque. The dihydropyridine derivative, nifedipine, has a marked effect on NM myosin expression and SMC differentiation in vitro. In vivo, short term administration of nifedipine resulted in the disappearance of 'immature' type SMCs from the aortic media of both normocholesterolaemic and hypercholesterolaemic adult rabbits. Moreover, in a model of atherosclerosis prevention, nifedipine significantly reduced the area of aortic intimal thickening and reduced the size of the 'immature' type SMC population both in the aortic media and intima of the hypercholesterolaemic rabbit.
Pauletto
P
P
Istituto di Medicina Clinica, Università di Padova, Italy.
Da Ros
S
S
Zoleo
M
M
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009218:Myosins / Q000032:analysis; D009543:Nifedipine / Q000494:pharmacology*
D009218:Myosins; D009543:Nifedipine