Therapeutic approaches to the control of coronary atherosclerosis
Atherosclerosis is a multifactorial disease which culminates in the ruptured plaque seen at autopsy. Hypercholesterolaemia, subintimal accumulation of lipid, monocyte adhesion followed by penetration across the endothelium, the conversion of monocytes to macrophages and smooth muscle cell proliferation and migration are some of the events involved in the early stages of lesion formation. Late events include the formation of excess ground substance and collagen, and the formation of the fibrotic cap. Young lesions tend to be more fragile than “old” calcified lesions, and it is these young lesions which rupture, haemorrhage and provide anchor points for platelets.
Therapeutic interventions aimed at controlling lesion formation include those which reduce risk factors, including hypertension as well as those which interfere with the cascade of events involved in lesion formation. Agents which lower plasma cholesterol provide one approach. Another approach is to use calcium antagonists which not only lower blood pressure, but also directly interfere with some of the metabolic events involved in lesion formation.
Key wordsCalcium antagonists Nifedipine Nisoldipine Cholesterol Atherogenesis oxyradicals
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- 3.Fuster V, Stein B, Ambrose JA, Badimon I, Badimon JJ, Chesbro JH (1990) Atherosclerotic plaque rupture and thrombis: evolving concepts. Circulation 82 (Suppl II): 11–47–11–59Google Scholar
- 4.Gottlieb SO, Brinker JA, Mellitis ED, Aschuff SC, Baughman KL. Traill TA, Weiss JL, Reitz BA, Weisfeldt M, Gerstenblith G (1989) Effect of nifedipine on the development of coronary bypass graft stenosis in high-risk patients: a randomized double-blind, placebo- controlled trial. Circulation 80 (Suppl 2) 11–228 (abstract)Google Scholar
- 9.Nayler WG (1991) Molecular mechanisms involved in the anti-atherogenic effect of the calcium antagonists. In: Nayler WG, The Second Generation of Calcium Antagonists, Springer Verlag, Berlin, pp 139–151Google Scholar
- 10.Nayler WG, Pangiotopoulos S (1986) Calcium antagonism. In: Kelly DT(ed) Proceedings of II Asian Pacific Adalat Symposium, ADIS Press, New Zealand, pp 3–11Google Scholar
- 11.Neuser D, Rosen B (1990) Calcium antagonists and the proliferation of vascular smooth muscle cells. Satellite Symposium of 13th ISH meeting Montreal “Antiatherosclerotic Potential of Calcium Antagonists” pp 9–10Google Scholar
- 13.Orekov AN, Tertov VU, Khashimov KA, Kudryashou SA, Smirnov VN (1986) Anti- atherosclerotic effects of verapamil in primary culture of human aortic intimal cells. J Hypertens 4 (Suppl 6): S 153–155Google Scholar
- 19.Stein O, Stein Y (1987) Effect of verapamil on cholesteryl ester hydrolysis and re-esteiifica- tion in macrophages. Atherosclerosis 7: 578–584Google Scholar
- 20.Stein O, Halpenis G, Stein Y (1987) Long term effects of verapamil on aortic smooth muscle cells cultured in the presence of hypercholesterolaemic serum. Atherosclerosis 7: 585–592Google Scholar
- 23.Waters D, Lesperance J, Francetich M, Causey D, Theroux P, Chiang Y-K, Hudon G, Lemarbre L, Reitman M, Joyal M, Gosselin G, Dyrda I, Macer J, Havel RJ (1990) A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis. Circulation 82: 1940–1953PubMedCrossRefGoogle Scholar