Specific cellular features of atheroma associated with development of neointima after carotid endarterectomy: the carotid atherosclerosis and restenosis study.

BACKGROUND: The purpose of this study was to investigate whether some cellular and molecular features of tissue retrieved at carotid endarterectomy are associated with the extent of neointima formation at ultrasound follow-up. METHODS AND RESULTS: One hundred fifty patients were studied. Endarterectomy specimens were tested by immunocytochemistry with the use of (1) monoclonal antibodies that identify smooth muscle cells (SMCs) and fetal-type SMCs on the basis of smooth muscle and nonmuscle myosin content, (2) the anti-macrophage HAM 56, and (3) the anti-lymphocyte CD45RO. The maximum intima-media thickness (M-IMT) of the revascularized vessel was assessed by the use of B-mode ultrasonography 6 months after surgery. The M-IMT values were related positively to the number of SMCs (r=0.534, P<0.0005) and negatively to that of macrophages and lymphocytes (r=-0.428, P<0.0005, and -0.538, P=0.001, respectively). Patients were classified as class 1 (M-IMT 1.3 mm). An abundance of SMCs, mostly of fetal type, was found in the plaque of class 3 patients, whereas lesions from class 1 patients were rich in macrophages and lymphocytes. In the multivariate analysis, factors related to M-IMT were the number of SMCs and the percentage of fetal-type SMCs present in the plaque. CONCLUSIONS: Although the classic risk factors did not play a role, an abundance of SMCs and a scarcity of macrophages characterized the primary lesion of patients in whom neointima developed after surgery. In patients in whom neointima did not develop, lesions were rich in macrophages and lymphocytes. This approach can be useful in defining patients at risk of restenosis.

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.

Human cytomegalovirus and restenosis of the internal carotid artery.

BACKGROUND: Although human cytomegalovirus (HCMV) has been implicated in coronary restenosis, data on the presence of HCMV in the restenosis lesion of the internal carotid artery (ICA) are lacking. SUMMARY OF REPORT: We studied endarterectomy tissue from 5 ICA restenosis and 5 primary atherosclerotic lesions and tissue from 5 normal ICAs. The extracted DNA was tested for HCMV sequences with polymerase chain reaction by use of three primer pairs that amplify different genomic regions. The AD 169 strain of HCMV served as the positive control. No trace of the HCMV genome was found in the intima or in the underlying media of endarterectomy specimens from restenosis and primary lesions. The media from control arteries was also HCMV negative. CONCLUSIONS: At variance with previous studies carried out in coronary arteries, our results do not support the hypothesis that HCMV infection is implicated in restenosis of the ICA.