Valvular osteoclasts in calcification and aortic valve stenosis severity (original) (raw)
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European Heart Journal, 2013
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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.
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)
Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves
International Journal of Cardiology, 2010
Background: Emerging evidence suggests that calcific aortic valve stenosis constitutes an active process sharing common features with atherosclerosis and bone formation. To further support this hypothesis, we investigated the expression of bone regulatory factors in calcified aortic valves. Methods-results: Formalin-fixed, paraffin-embedded tissue samples of human aortic tricuspid valves (n = 54) were used from patients undergoing valve replacement for calcific, non-rheumatic aortic stenosis. As controls, fourteen aortic tricuspid valves (n = 14) were obtained at autopsy from patients without clinical and morphological aortic valve lesions. Sections from both stenotic and normal aortic valve leaflets were studied immunohistochemically. Interstitial cells in stenotic valves showed intense expression of Sox9, Runx2 and Osterix (Osx) whereas NFATc1 was expressed in interstitial and inflammatory cells. In addition, NFATc1 expression correlated significantly with Osx (r = 0.458, p b 0.001) and Runx2 (r = 0.387, p b 0.001). Finally, there was accumulation of activated interstitial cells, T lymphocytes and macrophages as well as intense neoangiogenesis in pathological leaflets. Conclusions: The presence of NFATc1 and Osx in our material lends further support to the hypothesis that during the process of aortic valve calcification there is expression of osteoblastic phenotypes by valvular cells.
European Heart Journal, 2010
Westernized countries face a growing burden of cardiovascular calcification and osteoporosis. Despite its vast clinical significance, the precise nature of this reciprocal relationship remains obscure. We hypothesize that cardiovascular calcification progresses with inflammation and inversely correlates with bone tissue mineral density (TMD). Methods and results Arterial, valvular, and bone metabolism were visualized using near-infrared fluorescence (NIRF) molecular imaging agents, targeting macrophages and osteogenesis. We detected significant arterial and aortic valve calcification in apoE 2/2 mice with or without chronic renal disease (CRD, 30 weeks old; n ¼ 28), correlating with the severity of atherosclerosis. We demonstrated decreases in osteogenic activity in the femurs of apoE 2/2 mice when compared with WT mice, which was further reduced with CRD. Three-dimensional micro-computed tomography imaging of the cortical and cancellous regions of femurs quantified structural remodelling and reductions in TMD in apoE 2/2 and CRD apoE 2/2 mice. We established significant correlations between arterial and valvular calcification and loss of TMD (R 2 ¼ 0.67 and 0.71, respectively). Finally, we performed macrophage-targeted molecular imaging to explore a link between inflammation and osteoporosis in vivo. Although macrophage burden, visualized as uptake of NIRF-conjugated iron nanoparticles, was directly related to the degree of arterial and valvular inflammation and calcification, the same method inversely correlated inflammation with TMD (R 2 ¼ 0.73; 0.83; 0.75, respectively). Conclusion This study provides direct in vivo evidence that in arteries and aortic valves, macrophage burden and calcification associate with each other, whereas inflammation inversely correlates with bone mineralization. Thus, understanding inflammatory signalling mechanisms may offer insight into selective abrogation of divergent calcific phenomena.