The lipid theory in the pathogenesis of calcific aortic stenosis

被引:70
作者
Parisi, V. [1 ]
Leosco, D. [1 ]
Ferro, G. [1 ]
Bevilacqua, A. [1 ]
Pagano, G. [1 ]
de Lucia, C. [1 ]
Filardi, P. Perrone [2 ]
Caruso, A. [3 ]
Rengo, G. [1 ,4 ]
Ferrara, N. [1 ,4 ]
机构
[1] Univ Naples Federico II, Dipartimento Sci Med Traslaz, I-80131 Naples, Italy
[2] Univ Naples Federico II, Dipartimento Sci Biomed Avanzate, I-80131 Naples, Italy
[3] Casa Cura S Michele, Maddaloni, Italy
[4] Ist Telese Terme, Fdn S Maugeri, IRCCS, Turin, BN, Italy
关键词
Aortic valve stenosis; Lipids; RANK; Statins; Physical activity; LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; BONE-MINERAL DENSITY; ANGIOTENSIN-CONVERTING ENZYME; REGULAR PHYSICAL-ACTIVITY; VALVE CALCIFICATION; VASCULAR CALCIFICATION; RECEPTOR; PROGRESSION; ASSOCIATION;
D O I
10.1016/j.numecd.2015.02.001
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Aims: 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). Data synthesis: 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/RANKL/Osteprotegerin, which induce the transition of valvular myofibroblasts toward an osteogenic phenotype with consequent valvular bone deposition. Although all these evidence strongly support the lipid theory in AS pathogenesis, lipids lowering therapies failed to demonstrate in controlled trials a significant efficacy to slow AS progression. Encouraging results from animal studies indicate that physical activity may counteract the biological processes inducing AV degeneration. Conclusions: This review indicates a robust interplay between lipids, inflammation, and calcific AS. This new pathophysiological scenario of such an emerging valvular disease paves the way to the next challenge of cardiovascular research: "prevent and care aortic valve stenosis". (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:519 / 525
页数:7
相关论文
共 77 条
[1]
Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease [J].
Adams, V ;
Linke, A ;
Kränkel, N ;
Erbs, S ;
Gielen, S ;
Möbius-Winkler, S ;
Gummert, JF ;
Mohr, FW ;
Schuler, G ;
Hambrecht, R .
CIRCULATION, 2005, 111 (05) :555-562
[2]
Aortic valve calcification: association with bone mineral density and cardiovascular risk factors [J].
Aksoy, Y ;
Yagmur, C ;
Tekin, GO ;
Yagmur, J ;
Topal, E ;
Kekilli, E ;
Turhan, H ;
Kosar, F ;
Yetkin, E .
CORONARY ARTERY DISEASE, 2005, 16 (06) :379-383
[3]
[Anonymous], REVEAL RAND EV EFF A
[4]
[Anonymous], LANCET
[5]
[Anonymous], 2014, J AM COLL CARDIOL, V63
[6]
Ardehali R, 2012, J HEART VALVE DIS, V21, P337
[7]
Amyloid substance within stenotic aortic valves promotes mineralization [J].
Audet, Audrey ;
Cote, Nancy ;
Couture, Christian ;
Bosse, Yohan ;
Despres, Jean-Pierre ;
Pibarot, Philippe ;
Mathieu, Patrick .
HISTOPATHOLOGY, 2012, 61 (04) :610-619
[8]
Wnt signaling and osteoblastogenesis [J].
Bodine, Peter V. N. ;
Komm, Barry S. .
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS, 2006, 7 (1-2) :33-39
[9]
Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis [J].
Briand, Martin ;
Lemieux, Isabelle ;
Dumesnil, Jean G. ;
Mathieu, Patrick ;
Cartier, Amelie ;
Despres, Jean-Pierre ;
Arsenault, Marie ;
Couet, Jacques ;
Pibarot, Philippe .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 47 (11) :2229-2236
[10]
Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits [J].
Busseuil, D. ;
Shi, Y. ;
Mecteau, M. ;
Brand, G. ;
Kernaleguen, A-E ;
Thorin, E. ;
Latour, J-G ;
Rheaume, E. ;
Tardif, J-C .
BRITISH JOURNAL OF PHARMACOLOGY, 2008, 154 (04) :765-773