Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 139, Issue 1, Pages 2-6Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2009.05.019
Keywords
Synergy; Calcium channel blockers; Statins; Hypothesis
Categories
Funding
- British Heart Foundation
- Foundation for Circulatory Health
- NIHR Biomedical Research Centre
- National Institute for Health Research [NF-SI-0508-10116] Funding Source: researchfish
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In the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) we have reported a positive interaction between atorvastatin and amlodipine-based antihypertensive strategy in terms of the prevention of coronary events. In cellular and molecular studies on human vascular smooth muscle cells (VSMC) we have reported that transformation from a differentiated to a synthetic or dedifferentiated phenotype is associated with loss of function of L-type calcium channels and hence loss of potential responsiveness to calcium channel blockers (CCB). Statins directly inhibit cell cycle progression and dedifferentiation of VSMC due to their ability to inhibit the synthesis of isoprenoid cholesterol intermediates. We hypothesize that statins promote a more differentiated VSMC phenotype that results in upregulation of L-type calcium channels and restoration of a CCB-sensitive calcium influx pathway in VSMC, favourably affecting the balance that exists between VSMC proliferation, apoptosis and matrix metalloproteinase production with an associated increase in stability of atheromatous plaques. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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