title: Calcific Aortic Valve Disease: Part 1--Molecular Pathogenetic Aspects, Hemodynamics, and Adaptive Feedbacks.
abstract: Aortic valvular stenosis (AVS), produced by calcific aortic valve disease (CAVD) causing reduced cusp opening, afflicts mostly older persons eventually requiring valve replacement. CAVD had been considered "degenerative," but newer investigations implicate active mechanisms similar to atherogenesis--genetic predisposition and signaling pathways, lipoprotein deposits, chronic inflammation, and calcification/osteogenesis. Consequently, CAVD may eventually be controlled/reversed by lifestyle and pharmacogenomics remedies. Its management should be comprehensive, embracing not only the valve but also the left ventricle and the arterial system with their interdependent morphomechanics/hemodynamics, which underlie the ensuing diastolic and systolic LV dysfunction. Compared to even a couple of decades ago, we now have an increased appreciation of genomic and cytomolecular pathogenetic mechanisms underlying CAVD. Future pluridisciplinary studies will characterize better and more completely its pathobiology, evolution, and overall dynamics, encompassing intricate feedback processes involving specific signaling molecules and gene network cascades. They will herald more effective, personalized medicine treatments of CAVD/AVS.
authors.affiliation: Duke University School of Medicine, Durham, NC, USA. apasipou@duke.edu.|Duke/NSF Research Center for Emerging Cardiovascular Technologies, Durham, NC, USA. apasipou@duke.edu.|Duke University Graduate School, Durham, NC, 27710, USA. apasipou@duke.edu.
authors.forename: Ares
authors.initials: A
authors.lastname: Pasipoularides
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D025461:Feedback, Physiological; D020022:Genetic Predisposition to Disease; D006439:Hemodynamics; D006801:Humans; D040542:Mechanotransduction, Cellular; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D016277:Ventricular Function, Left
keywords: Aortic transvalvular pressure gradient; Aortic valve inflammation, fibrosis and calcific nodule buildup; Aortic valvular stenosis (AVS); Bicuspid aortic valve disease (BAVD); Compensatory myocardial hypertrophy in pressure overload (PO); Feedback control of myocardial hypertrophy; Fetal type genes; Genomics of calcific aortic valve disease (CAVD); Hemodynamics; Immediate early-response genes (IEGs); Intrinsic component of the total systolic ventricular load; Macromolecular crowding and cardiomyocyte diameters in PO hypertrophy; Pressure loss recovery; Replication of cardiomyocyte sarcomeres in-parallel and in-series