Review: the central role of calcium in the pathogenesis of cardiovascular disease.

Calcium-dependent processes play a central role in several different cells of the cardiovascular system including vascular smooth muscle and endothelial cells and also in monocytes, macrophages and platelets. In response to extracellular stimuli cytosolic calcium concentration increases. The increase is composed of two distinct phases. Firstly, calcium is released from intracellular stores via IP3. In the second phase calcium influx across the cell membrane is mostly responsible for the sustained rise in intracellular calcium concentration. This phase of the peak increase in cytosolic calcium is a prerequisite for sustained activation of the cell and the processes of vascular smooth muscle contraction and the activation of nuclear transcription factors for protein biosynthesis. Under ischemic conditions the regulatory systems which control the intracellular free calcium concentration consume a major portion of the cell's physiological energy supply (90%) and a decreased oxygen supply under ischemic conditions rapidly reduces the cell's capacity for intracellular calcium storage or outward transport across its membrane. Calcium antagonist drugs principally act on L-type calcium channels to reduce the influx of calcium into the the cells of the body. Since calcium antagonist drugs are able to influence a wide range of cellular processes which have been implicated in atherosclerosis, glomeruloscierosis, left ventricular hypertrophy and insulin resistance there are strong grounds for their use in a range of clinical disease states.