Another Calcium Paradox?

In a number of important diseases, the clinical course is defined principally by the host response, more so than by the initiating environmental insult. Clinicians rely on identification of this host response for diagnosis and may select those responses as targets for therapeutic intervention. Atherosclerosis is one such disease. The clinical course was once felt to result from progressive accumulation of inert “deposits” of cholesterol and calcium. In the past decade, it has become clear and widely understood that atherosclerosis is a complex orchestrated series of host responses to as yet poorly understood vascular injury.1 One of the most striking and convincing mechanistic advances in recent times has been the revelation of the extent to which inflammatory events predominate in the afflicted arterial wall.2 This understanding has been reached by basic and clinical studies at the tissue, cellular, and subcellular levels3 and by population-based epidemiological investigations.4 The atherosclerotic process can be viewed as occurring in stages, beginning with a “nascent” period, during which fatty streaks appear in the arterial wall.1 Transformation to a “hot” phase ensues, consisting of accumulation of free lipid, leukocyte attraction and activation, and proliferation of arterial wall cells.5 This phase, the paradigm holds, gives way to lipid resorption, collagen deposition and remodeling, and calcification of vessel wall tissue.6 We now know that mural calcification, once thought to represent a “burned out” stage of atherosclerosis, is actually a complex programmed …