title: The lipid theory in the pathogenesis of calcific aortic stenosis.
abstract: OBJECTIVE
  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).
  
  
  RESULTS
  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".
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy.
authors: V
authors: V
authors: Parisi
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy. Electronic address: dleosco@unina.it.
authors: D
authors: D
authors: Leosco
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy.
authors: G
authors: G
authors: Ferro
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy.
authors: A
authors: A
authors: Bevilacqua
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy.
authors: G
authors: G
authors: Pagano
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy.
authors: C
authors: C
authors: de Lucia
authors: Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli Federico II, Italy.
authors: P
authors: P
authors: Perrone Filardi
authors: Casa di Cura S. Michele, Maddaloni, Italy.
authors: A
authors: A
authors: Caruso
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy; Fondazione S. Maugeri, IRCCS, Istituto di Telese Terme, BN, Italy.
authors: G
authors: G
authors: Rengo
authors: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli Federico II, Italy; Fondazione S. Maugeri, IRCCS, Istituto di Telese Terme, BN, Italy.
authors: N
authors: N
authors: Ferrara
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D050197:Atherosclerosis / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D016723:Bone Remodeling; D002114:Calcinosis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators
keywords: Aortic valve stenosis; Lipids; Physical activity; RANK; Statins