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Libby P, Schwartz D, Brogi E, et al. A cascade model for restenosis. A special case of atherosclerosis progression. Circulation. 1992;86(6):III47-52
Libby, P., Schwartz, D., Brogi, E., Tanaka, H., & Clinton, S. K. (1992). A cascade model for restenosis. A special case of atherosclerosis progression. Circulation, 86(6), III47-52.
Libby, P, et al. "A cascade model for restenosis. A special case of atherosclerosis progression." Circulation vol. 86,6 (1992): III47-52.
Libby P, Schwartz D, Brogi E, Tanaka H, Clinton SK. A cascade model for restenosis. A special case of atherosclerosis progression. Circulation. 1992 Dec;86(6):III47-52. PMID: 1424051.
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Circulation. 1992 Dec;86(6):III47-52.

A cascade model for restenosis. A special case of atherosclerosis progression.

Circulation

P Libby, D Schwartz, E Brogi, H Tanaka, S K Clinton

Affiliations

  1. Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.

PMID: 1424051

Abstract

BACKGROUND: Restenosis presently limits the long-term success of percutaneous transluminal coronary angioplasty (PTCA) and allied treatments of atheroma. Current views of the pathophysiology of restenosis fail to explain certain important clinical features: Thrombosis, often invoked as a cause of smooth muscle proliferation, wanes before intimal thickening peaks. Prolonged antithrombotic therapy does not eliminate restenosis after PTCA. Furthermore, only a minority of angioplastied lesions develop clinically significant restenosis.

METHODS AND RESULTS: We propose a cytokine-growth factor cascade mechanism of restenosis pathobiology that could explain these features of human restenosis. According to this model, PTCA would produce acute local thrombosis and/or mechanical injury that triggers cytokine/growth factor gene expression by resident macrophages and smooth muscle cells. This early acute generation of cytokines could evoke a secondary growth factor and cytokine response that might establish a positive, self-stimulatory autocrine and paracrine feedback loop that would serve to amplify and sustain the proliferative response. This multistage schema would account for the lag between injury and restenosis and the failure of chronic antithrombotic therapy to prevent this process. Human atheromata contain variable numbers of macrophages. The macrophage content of a particular lesion could determine in part propensity to develop restenosis after angioplasty, explaining why all lesions do not develop this process.

CONCLUSIONS: Several experimental observations support this novel mechanistic model. Leukocytes and smooth muscle cells express genes for cytokines and growth factors, and products of coagulation and thrombosis can activate mononuclear phagocytes. Cytokines and growth factors often augment their own gene expression and induce one another, providing a potential intralesional amplification loop. Experimental atheroma and advanced human atherosclerotic lesions do not express high levels of growth-stimulatory cytokines such as interleukin-1 or tumor necrosis factor in the basal state but exhibit inducible expression in response to an injurious stimulus. Thus, cascades of autocrine or paracrine mediators whose expression is triggered by vascular injury might contribute to deranged smooth muscle behavior during restenosis.

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