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The antiatherogenic potential of calcium antagonists
1Department of Lipid and Lipoprotein Metabolism, Sandoz Research Institute, East Hanover, NJ 07936.
Abstract:
Atherosclerosis is an arterial disease characterized by focal accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolic function. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium channel blockers can reduce the accumulation of atherogenic lesion components and thus apparently decrease the progression of lesions. Although there are some conflicting data in the animal model studies using calcium channel antagonists, as a result of differences in experimental designs, it is now apparent that several classes of calcium channel blockers inhibit the progression of early arterial lesions induced by cholesterol feeding. The dihydropyridine calcium channel blockers appear to be more potent antiatherosclerotic agents than other classes of calcium channel antagonists. Several mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolic functions may be responsible for the calcium channel blocker effects on early lesion progression. For example, recent studies in cell culture model systems suggest that calcium channel blockers may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium channel blockers may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium-independent metabolic activities.
Insights
Calcium channel blockers, particularly dihydropyridines, show potential in reducing atherosclerosis progression by inhibiting arterial lesion development. These agents may work by managing calcium levels and influencing cellular metabolism.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Atherosclerosis involves arterial buildup of lipids, calcium, and other substances, linked to macrophages and smooth muscle dysfunction.
- Animal models, particularly cholesterol-fed rabbits, suggest calcium-modulating agents can slow lesion development.
Purpose of the Study:
- To evaluate the anti-atherosclerotic effects of calcium channel blockers (CCBs).
- To investigate the mechanisms underlying CCB action on early arterial lesion progression.
Main Methods:
- Review of studies using animal models (e.g., cholesterol-fed rabbits) and cell culture systems.
- Analysis of data on calcium competitors, chelators, anticalcifying agents, and CCBs.
Main Results:
- Several CCB classes inhibit the progression of early arterial lesions in cholesterol-fed animals.
- Dihydropyridine CCBs appear more potent as anti-atherosclerotic agents.
- CCBs may reduce lesion progression via calcium-dependent and calcium-independent mechanisms affecting cellular metabolism.
Conclusions:
- CCBs demonstrate anti-atherosclerotic properties, impacting early lesion development.
- Both calcium flux modulation and calcium-independent metabolic alterations contribute to CCB efficacy.
- Dihydropyridines represent a promising class of CCBs for managing atherosclerosis.