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Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury.
Proc Natl Acad Sci U S A. 1993 Jul 01; 90(13):6189-93.PN

Abstract

Carvedilol is a cardiovascular drug currently used for the treatment of hypertension. Clinical studies have recently demonstrated efficacy in angina and congestive heart failure. Recently, carvedilol has been shown to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis induced by a wide variety of growth factors. These findings are of interest since smooth muscle proliferation and abnormal lipid metabolism are proposed to play an important role in the pathogenesis of atherosclerotic plaque formation and in development of stenotic lesions following vascular injury by balloon angioplasty and coronary artery bypass grafting. On the basis of these observations, the antiproliferative actions of carvedilol have been explored in detail. In human cultured pulmonary artery vascular smooth muscle cells, carvedilol (0.1-10 microM) produced a concentration-dependent inhibition of the mitogenesis stimulated by platelet-derived growth factor, epidermal growth factor, thrombin, and serum, with IC50 values ranging from 0.3 to 2.0 microM. Carvedilol also produced a concentration-dependent inhibition of vascular smooth muscle cell migration induced by platelet-derived growth factor, with an IC50 value of 3 microM. The extensive neointimal formation that occurs following balloon angioplasty of rat carotid arteries was markedly attenuated by carvedilol (1 mg/kg, i.p.; twice daily starting 3 days before angioplasty and continuing until 14 days after angioplasty). Quantitative image analysis demonstrated that carvedilol reduced the neointimal growth following angioplasty by 84% without altering either medial or adventitial cross-sectional areas. These observations indicate that carvedilol may also be effective in the treatment of pathological disorders principally associated with abnormal vascular smooth muscle growth, such as atherosclerosis and acute vascular wall injury induced by angioplasty or coronary artery bypass grafting.

Authors+Show Affiliations

Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8327499

Citation

Ohlstein, E H., et al. "Carvedilol, a Cardiovascular Drug, Prevents Vascular Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation Following Vascular Injury." Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 13, 1993, pp. 6189-93.
Ohlstein EH, Douglas SA, Sung CP, et al. Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury. Proc Natl Acad Sci U S A. 1993;90(13):6189-93.
Ohlstein, E. H., Douglas, S. A., Sung, C. P., Yue, T. L., Louden, C., Arleth, A., Poste, G., Ruffolo, R. R., & Feuerstein, G. Z. (1993). Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury. Proceedings of the National Academy of Sciences of the United States of America, 90(13), 6189-93.
Ohlstein EH, et al. Carvedilol, a Cardiovascular Drug, Prevents Vascular Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation Following Vascular Injury. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6189-93. PubMed PMID: 8327499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury. AU - Ohlstein,E H, AU - Douglas,S A, AU - Sung,C P, AU - Yue,T L, AU - Louden,C, AU - Arleth,A, AU - Poste,G, AU - Ruffolo,R R,Jr AU - Feuerstein,G Z, PY - 1993/7/1/pubmed PY - 2001/3/28/medline PY - 1993/7/1/entrez SP - 6189 EP - 93 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 90 IS - 13 N2 - Carvedilol is a cardiovascular drug currently used for the treatment of hypertension. Clinical studies have recently demonstrated efficacy in angina and congestive heart failure. Recently, carvedilol has been shown to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit vascular smooth muscle mitogenesis induced by a wide variety of growth factors. These findings are of interest since smooth muscle proliferation and abnormal lipid metabolism are proposed to play an important role in the pathogenesis of atherosclerotic plaque formation and in development of stenotic lesions following vascular injury by balloon angioplasty and coronary artery bypass grafting. On the basis of these observations, the antiproliferative actions of carvedilol have been explored in detail. In human cultured pulmonary artery vascular smooth muscle cells, carvedilol (0.1-10 microM) produced a concentration-dependent inhibition of the mitogenesis stimulated by platelet-derived growth factor, epidermal growth factor, thrombin, and serum, with IC50 values ranging from 0.3 to 2.0 microM. Carvedilol also produced a concentration-dependent inhibition of vascular smooth muscle cell migration induced by platelet-derived growth factor, with an IC50 value of 3 microM. The extensive neointimal formation that occurs following balloon angioplasty of rat carotid arteries was markedly attenuated by carvedilol (1 mg/kg, i.p.; twice daily starting 3 days before angioplasty and continuing until 14 days after angioplasty). Quantitative image analysis demonstrated that carvedilol reduced the neointimal growth following angioplasty by 84% without altering either medial or adventitial cross-sectional areas. These observations indicate that carvedilol may also be effective in the treatment of pathological disorders principally associated with abnormal vascular smooth muscle growth, such as atherosclerosis and acute vascular wall injury induced by angioplasty or coronary artery bypass grafting. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/8327499/Carvedilol_a_cardiovascular_drug_prevents_vascular_smooth_muscle_cell_proliferation_migration_and_neointimal_formation_following_vascular_injury_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8327499 DB - PRIME DP - Unbound Medicine ER -