| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Restenosis after an initial successful percutaneous transluminal coronary angioplasty (PTCA) occurs in 30-40% of patients and thus remains a significant clinical problem. In the vast majority, a fibrocellular tissue reaction with smooth muscle cells, as the prime cellular component, is the underlying morphologic substrate of restenosis.
Migration and proliferation of smooth muscle cells as well as synthesis of extracellular matrix components, relate closely to their cytoskeletal features. Most information thus far has been obtained from experimental studies, and the mechanisms that underlie migration and proliferation of human smooth muscle cells are unclear still.
The present study demonstrates, for the first time, that both PDGE-A and PDGF-B chain mRNAs are expressed at sites of repair in human coronary arteries after PTCA (Ueda M et al. Am J Pathol 1996). This study also shows the expression of PDGF-B and PDGF-beta receptor proteins at sites of postangioplasty repair in humans (Tanizawa S et al. Heart 1996). These findings strongly suggest that PDGF is involved in the process of migration and proliferation of smooth muscle cells in human coronary arteries.
The present study, moreover, documents that up-regulation of tenascin may play a role in the migration and phenotypic modulation of smooth muscle cels in humans (Tanabe S et al. Transpl Int 1996). The present study also demonstrates, for the first time, that C-type natriuretic peptide (CNP), which is a potent inhibitor of smooth muscle cells, is expressed in intimal cells of human coronary arteries, and has functional significance in atherogenesis (Naruko T et al. Circulation 1996). Finally, our study shows that, during smooth muscle cell migration and proliferation at the site of PTCA,smooth muscle cells show features of an undifferentiated state, indicated by altered expression of smooth muscle myosin heavy chain (Aikawa M et at., Circulation in press).
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