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Effects of calcium antagonists on atherogenesis
W Kiowski1, P Erne, F R Bühler
1Department of Internal Medicine, Kantonsspital Basel, Switzerland.
Abstract:
Calcium antagonists are able to reduce the development of atherosclerotic lesions in many animal models of atherosclerosis. Although the precise mechanisms of their antiatherogenic effects are unknown studies have shown interference with several pathogenetic mechanisms of the atherosclerotic disease process, namely preservation of endothelial integrity, reduced smooth muscle cell migration and proliferation, increased low density lipoprotein uptake and degradation in smooth muscle cells and reduced synthesis of matrix components. Many of these effects are unrelated to their blocking effects on voltage-dependent slow calcium channels, and most effects have been observed with very high concentrations only. Furthermore, differing calcium antagonists seem to influence these mechanisms differently but available data are difficult to interpret because of differences in study design and models used. With the exception of data on calcium antagonists for secondary prevention after myocardial infarction and their influence on the rate of restenosis after percutaneous transluminal angioplasty, no data are available in man with respect to a possible influence on atherosclerosis. Results from on-going studies designed to address specifically this issue must be awaited to answer the question whether the experimental findings can be extended to human atherosclerosis.
Insights
Calcium antagonists show potential in reducing atherosclerosis development in animal models by impacting various disease mechanisms. However, human data is limited, and further studies are needed to confirm these antiatherogenic effects in humans.
Area of Science:
- Cardiovascular Research
- Pharmacology
Background:
- Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
- Calcium antagonists have demonstrated antiatherogenic effects in numerous animal models.
- The precise mechanisms underlying these effects remain largely unknown.
Purpose of the Study:
- To investigate the potential antiatherogenic effects of calcium antagonists.
- To explore the mechanisms by which calcium antagonists may influence the atherosclerotic disease process.
- To evaluate the current evidence regarding calcium antagonists and human atherosclerosis.
Main Methods:
- Review of existing studies on calcium antagonists and atherosclerosis in animal models.
- Analysis of proposed pathogenetic mechanisms, including endothelial integrity, smooth muscle cell behavior, and lipoprotein metabolism.
- Assessment of available human data, primarily focusing on secondary prevention post-myocardial infarction and restenosis rates.
Main Results:
- Calcium antagonists interfere with key atherosclerotic mechanisms such as endothelial integrity, smooth muscle cell migration/proliferation, and low-density lipoprotein handling.
- Many observed effects are independent of calcium channel blockade and occur at high concentrations.
- Data interpretation is challenging due to variations in study design and models used.
- Limited human data exists, with some evidence from post-myocardial infarction and angioplasty studies.
Conclusions:
- Experimental findings suggest calcium antagonists possess antiatherogenic properties.
- The translation of these findings to human atherosclerosis requires further investigation.
- Results from ongoing human studies are crucial to determine the clinical relevance of calcium antagonists in managing atherosclerosis.