Calcification in atherosclerosis: Bone biology and chronic inflammation at the arterial crossroads

Abstract

Dystrophic or ectopic mineral deposition occurs in many pathologic conditions, including atherosclerosis. Calcium mineral deposits that frequently accompany atherosclerosis are readily quantifiable radiographically, serve as a surrogate marker for the disease, and predict a higher risk of myocardial infarction and death. Accelerating research interest has been propelled by a clear need to understand how plaque structure, composition, and stability lead to devastating cardiovascular events. In atherosclerotic plaque, accumulating evidence is consistent with the notion that calcification involves the participation of arterial osteoblasts and osteoclasts. Here we summarize current models of intimal arterial plaque calcification and highlight intriguing questions that require further investigation. Because atherosclerosis is a chronic vascular inflammation, we propose that arterial plaque calcification is best conceptualized as a convergence of bone biology with vascular inflammatory pathobiology.P laque structure and composition importantly impact clinical expression of atherosclerosis. Molecular medicine in the 21st century has turned toward a comprehensive understanding of the dynamic processes that influence the composition and stability of atheroma and of how structural plaque components impact clinical outcomes. Recently, increasing interest has focused on understanding how atherosclerotic pathology is related to a common plaque constituent: calcium mineral deposits. Pathologists have long known that calcified atherosclerotic arteries can contain tissue that is histomorphologically indistinguishable from bone (1, 2). Important studies in the last decade have now spawned a model wherein calcification in atherosclerotic plaque is viewed as an active, complex, and therefore presumably regulated process that exhibits intriguing similarities to new bone formation, or remodeling. Ectopic and dystrophic mineral deposition and extracellular matrix calcification can occur in numerous pathologic conditions by passive precipitation. Here we focus on one specific type of mineral deposition with high relevance to cardiac pathology: intimal arterial calcification in the context of atherosclerotic plaque. The emerging view is that plaque calcification represents a meeting of bone biology with chronic plaque inflammation. Remarkable cellular ontogenetic versatility in atherosclerosis appears to effect profound structural alterations, with significant ramifications for plaque stability and clinical outcomes. Clinical SignificanceAtherosclerotic lesions frequently become calcified. The process can begin early and accelerates as the disease progresses and more complex lesions develop. Calcium deposits in coronary arteries indicate the presence of plaque, but the converse statement that an absence of coronary calcium indicates an absence of atheromatous plaque is not true (1). Because calcification is a surrogate measure of coronary atherosclerosis, clinical interest has focused on the usefulness of noninvasive detection of calci...

Calcium and vitamin D intakes may be positively associated with brain lesions in depressed and nondepressed elders

“…Multiple mechanisms have been proposed to explain the etiology of vascular calcification, with bone biology, calcium homeostasis, and the inflammatory response having interactive roles [12,[43][44][45]. Specific mechanisms by which dietary calcium and vitamin D promote vascular calcification are unclear.…”

“…Calcium dysregulation is important in chronic diseases such as osteoporosis and atherosclerosis, as well as in nervous system disorders such as dementia and depression [9][10][11][12]. Calcification of vascular smooth muscle occurs with aging, renal disease, and atherosclerosis, and has been associated with brain lesions and cognitive impairment [13,14].…”

Influence of osteoclasts and osteoprotegerin on the mode of calcific degeneration of aortic valves

“…The regulatory role of osteoclastic-like cells in the maintenance of mineral homeostasis within the atherosclerotic arterial wall was postulated by Doherty et al 28 They suggested that vascular calcium deposition may be affected by the presence and activity of osteoclast-like cells, which are able to inhibit or even revert the ongoing calcification. However, mouse model studies indicated a procalcific influence of osteoclast-like cells on the cardiovascular system.…”

Vascular Calcifi cation in Chronic Kidney Disease

“…Ateroskleroz sürecinde rol alan kronik infl amasyon aynı zamanda vasküler kalsifi kasyona neden olan mekanizmaları da düzenlemektedir (6). Son dönemde yapılan çalışmalar VK gelişim sürecinde angiogenezin önemini ve osteoblast ve osteoklastların bu olaydaki etkilerini açıklığa kavuşturmuştur (7).…”