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  • Title: [Molecular and cellular mechanisms of arteriosclerosis and restenosis: possibilities of gene therapy].
    Author: Lüscher TF, Oemar BS, Yang Z, Noll G.
    Journal: Z Kardiol; 1996 Jul; 85(7):495-508. PubMed ID: 8928548.
    Abstract:
    Atherosclerosis and its consequences account for most of morbidity and mortality in Western countries. Atherosclerosis develops over a period of decades and has a complex pathogenesis. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it became clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation as well as vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the subintima as well as increased contraction, migration and proliferation of vascular smooth muscle cells. The fact that atherosclerosis develops only in certain, but not in other parts of the circulation, however, has rarely been considered. With the development of molecular biology techniques it became possible to clone differentially expressed genes in vessels with or without atherosclerosis; this in turn allows to better characterize the molecular and cellular mechanisms of the disease. The search for such candidate genes could set the basis for future genetic interventions. This therapeutic approach is likely to reach clinical importance particularly in monogenetic diseases (i.e., familial hypercholesterinemia), while its use in complex polygenetic diseases such as atherosclerosis is more difficult. Restenosis, however, may be accessible to gene therapy earlier on as it is amenable to local gene transfection.
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