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==Pathophysiology==
[[File:Cardiovascular calcification - Sergio Bertazzo.tif|thumbnail|right|Density-dependent colour scanning [[electron micrograph]] of cardiovascular calcification, showing in orange calcium phosphate spherical particles (denser material) and, in green, the extracellular matrix (less dense material).<ref name=":0">{{cite journal |vauthors=Bertazzo S, Gentleman E, Cloyd KL, Chester AH, Yacoub MH, Stevens MM |title=Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification |journal=Nature Materials |volume=12 |issue=6 |pages=576–83 |date=June 2013 |pmid=23603848 |pmc=5833942 |doi=10.1038/nmat3627|bibcode=2013NatMa..12..576B }}</ref>]]
The human [[aortic valve]] normally consists of three cusps or leaflets and has an opening of 3.0-4.0 square centimeters.<ref name="Cellular"/><ref name="Rare"/> When the left ventricle contracts, it forces blood through the valve into the aorta and subsequently to the rest of the body. When the left ventricle expands again, the aortic valve closes and prevents the blood in the aorta from flowing backward ([[aortic insufficiency|regurgitation]]) into the left ventricle. In aortic stenosis, the opening of the aortic valve becomes narrowed or constricted ([[stenosis|stenotic]]) (e.g., due to calcification). Degenerative (the most common variety), and bicuspid aortic stenosis both begin with damage to [[endothelial cell]]s from increased mechanical stress.<ref name="Thoughts">{{cite journal |last1=Rogers|first1=FJ|title=Aortic stenosis: new thoughts on a cardiac disease of older people|journal=Journal of the American Osteopathic Association|volume=113 |issue=11|pages=820–828 |date=November 2013|pmid=24174503|doi=10.7556/jaoa.2013.057|doi-access=free}}</ref><ref name="Rare"/> Inflammation is thought to be involved in the earlier stages of the pathogenesis of AS and its associated risk factors are known to promote the deposition of [[LDL cholesterol]] and [[lipoprotein(a)]], a highly damaging substance, into the aortic valve, causing significant damage and stenosis over time.<ref name="Thoughts"/><ref name="Rare"/>. Infiltration of inflammatory cells (macrophages, T lymphocytes), followed by the release of inflammatory mediators such as interleukin-1-beta and transforming growth factor beta-1 occurs.
Subsequently, fibroblasts differentiate into osteoblast-like cells, which results in abnormal bone matrix deposition leading to progressive valvular calcification and stenosis.<ref>Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001 Mar 20;103(11):1522-8. doi: 10.1161/01.cir.103.11.1522. PMID: 11257079.</ref>
As a consequence of this stenosis, the left ventricle must generate a higher pressure with each contraction to effectively move blood forward into the aorta.<ref name="Asymptomatic"/><ref name=Lilly>{{cite book | editor = Lilly LS | title = Pathophysiology of Heart Disease | edition = 3rd | publisher = Lippincott Williams & Wilkins | year = 2003 | isbn = 978-0-7817-4027-2 | url = https://archive.org/details/pathophysiologyo00lill }}</ref> Initially, the LV generates this increased pressure by thickening its muscular walls (myocardial hypertrophy). The type of hypertrophy most commonly seen in AS is known as concentric hypertrophy,<ref name="Asymptomatic"/> in which the walls of the LV are (approximately) equally thickened.
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