Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? (original) (raw)
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Calcification in Aortic Stenosis
Aortic stenosis is a common, potentially fatal condition that is set to become an increasing public health burden. Once symptoms develop, there is an inexorable deterioration with a poor prognosis. Despite this, there are no medical therapies capable of modifying disease progression, and the only available treatment is aortic valve replacement, to which not all patients are suited. Conventional teaching suggests that aortic stenosis is a degenerative condition whereby "wear and tear" leads to calcium deposition within the valve. Although mechanical stress and injury are important factors, it is becoming increasingly appreciated that aortic stenosis is instead governed by a highly complex, regulated pathological process with similarities to skeletal bone formation. This review discusses the pathophysiology of aortic stenosis with an emphasis on the emerging importance of calcification, how this can be visualized and monitored using noninvasive imaging, and how our improved knowledge may ultimately translate into novel disease-modifying treatments. (J Am Coll Cardiol 2015;66:561-77)
Aortic valve calcification: association with bone mineral density and cardiovascular risk factors
Coronary Artery Disease, 2005
Background Cardiovascular risk factors are reported to increase the incidence of aortic valve calcification. Among older women, low bone mineral density appears to be associated with increased prevalence of aortic calcification. We aimed to assess and compare cardiovascular risk factors and bone mineral density of patients with and without aortic valve calcification.
Calcific aortic stenosis: another face of atherosclerosis?
European Journal of Cardiovascular Prevention & Rehabilitation, 2006
ALCIFIC AORTIC STENOSIS has a lot in common with atherosclerotic coronary artery disease. So can lipid-lowering statin drugs stop it? Historically, calcific aortic stenosis was thought to result from aging and "wear and tear" of the aortic valve. 1,2 Hence it was designated "degenerative" or "senile-type." This perception is changing. Over the last decade, a growing understanding of the risk factors for calcific aortic stenosis and of its histologic characteristics have led to new insights into how it develops. Investigators have found histologic similarities between the lesion of aortic stenosis and atheromatous coronary artery disease 3,4 and have established an association between traditional atherosclerotic risk factors and the development of calcific aortic valve disease. 5-14 This condition is the most common reason for valve replacement in the United States, 15 and when it is severe it accounts for considerable disease and death, especially in older patients. Up to now, the only established treatment for symptomatic aortic valve stenosis has been to replace the valve. Newer therapies that may modify or reduce the likelihood of developing aortic valve disease are highly desirable and are currently under investigation. In this article we summarize what is known about the possible role of lipids, infection, and other risk factors in nonrheumatic calcific aortic sclerosis and stenosis and potential treatments. We use valve "sclerosis" to mean a thickening of the aortic valve leaflets, often with superimposed calcification, whereas valve "stenosis" implies a more advanced situation in which the leaflets stick and do not open normally.
European Journal of Vascular and Endovascular Surgery, 2005
Objectives. Vascular calcification is a complicating factor observed in advanced atherosclerosis. This review summarises the present knowledge regarding abdominal aortic calcification. Design. Literature review. Methods. A literature review was carried using MEDLINE and PUBMED with the search terms 'abdominal', 'aortic' and 'calcification'. Articles were assessed for data regarding mechanisms, measurement, risk factors and outcomes of aortic calcification.
Valvular osteoclasts in calcification and aortic valve stenosis severity
2013
Background: Bone remodeling in calcified aortic valves is thought to originate from microfractures at multiple sites of the valve, at which osteoclasts and osteoblasts are recruited. The aim of the present study was to assess circulating mediators of bone homeostasis, correlate them to the severity of stenosis and explore the spatio-temporal distribution of bone turnover in different parts of calcified aortic valve tissue. Methods and results: Plasma and explanted aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery. Plasma levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear-κB (RANK) ligand and Runt-related transcription factor 2 (Runx2/Cbfa1) exhibited a significant correlation to the severity of aortic stenosis. mRNA levels in normal, thickened and calcified parts of aortic valves assessed by quantitative real-time PCR were significantly elevated in calcified parts of valves for TRAP (5.08±1.6-fold, Pb 0.001) RANK ligand (8.6±4.2-fold, Pb 0.001) and RANK (1.98±0.78-fold, P=0.015). In an age, gender and aortic valve anatomy-adjusted multivariable regression analysis the local transcript levels of TRAP correlated significantly with echocardiographic parameters quantifying stenosis severity in early stages, whereas the expression level of Runx2/Cbfa1 was a predictor of the stenosis severity in advanced stages. Conclusions: These findings suggest a critical role of bone turnover as a determinant of aortic stenosis severity.
Calcification in atherosclerosis: Bone biology and chronic inflammation at the arterial crossroads
Proceedings of The National Academy of Sciences, 2003
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.
The lipid theory in the pathogenesis of calcific aortic stenosis
Nutrition, metabolism, and cardiovascular diseases : NMCD, 2015
Biologically active phenomena, triggered by atherogenesis and inflammation, lead to aortic valve (AV) calcification. Lipids play an important role in activating the cell signaling leading to AV bone deposition. This review, based on evidence from animal and human studies, mainly focused on the involvement of lipids and atherogenic phenomena in the pathogenesis of calcific aortic stenosis (AS). The role of elevated low density lipoproteins for the risk of both vascular atherosclerosis and AS has been elucidated. Lipid disorders act synergistically with other risk factors to increase prevalence of calcific AS. Atherosclerosis is also involved in the pathogenesis of bone demineralization, a typical hallmark of aging, which is associated with ectopic calcification at vascular and valvular levels. Animal studies have recently contributed to demonstrate that lipids play an important role in AS pathogenesis through the activation of molecular cell signalings, such as Wnt/Lrp5 and RANK/RANK...