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Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies

In atherosclerosis, the vascular smooth muscle cell (VSMC) contributes to vessel wall inflammation and lipoprotein retention, as well as to the formation of the fibrous cap that provides stability to the plaque. The VSMC can undergo a proliferative response that underlies the development of in-stent restenosis, bypass graft occlusion and transplant vasculopathy. Although the benefit/risk of therapeutic inhibition of VSMC proliferation in atherosclerosis is unclear, experimental and human evidence strongly suggests the therapeutic potential of antiproliferative therapy for in-stent restenosis, bypass graft failure and other vascular proliferative disorders.

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Figure 1: Function of VSMCs during different stages of atherosclerosis.

D. Maizels

Figure 2: Simplified scheme of the cell cycle.

D. Maizels

Figure 3: VSMCs mediate proliferation, inflammation, matrix alterations and contraction.

D. Maizels

Figure 4: Mechanisms of action of rapamycin and E2F decoy.

D. Maizels

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Acknowledgements

We thank S.M. Schwartz for suggestions and criticisms in the preparation of this manuscript. V.J.D. is the recipient of a National Heart Lung and Blood Institute MERIT Award. R.C.B.-D. is supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 547:A7, Graduiertenkolleg 534). D.G.S. is a scholar of the Deutsche Forschungsgemeinschaft (Graduiertenkolleg 534).

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Dzau, V., Braun-Dullaeus, R. & Sedding, D. Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies. Nat Med 8, 1249–1256 (2002). https://doi.org/10.1038/nm1102-1249

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