Amyloid substance within stenotic aortic valves promotes mineralization

Abstract

Apo-AI is a major component of amyloid substance present within CAVD valves. Furthermore, amyloid deposits participate in mineralization in CAVD by promoting apoptosis of valvular interstitial cells.

ApoB/ApoA‐I Ratio is Associated With Faster Hemodynamic Progression of Aortic Stenosis: Results From the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) Study

“…Interestingly, apoA‐I was also found in explanted stenotic aortic valves 33. The latter finding could be related to the modification of apoA‐I by proteins such as matrix metalloproteinases, increasing its affinity to proteoglycans, and altering its reverse cholesterol transport function, leading to its accumulation within tissues 33, 34, 35, 36. Therefore, this lipid accumulation and retention, may act as a “warning” signal triggering the pathophysiologic processes involved in the development and progression of AS 4, 37.…”

“…Experimental studies have reported an accumulation of apoB and several other apolipoproteins within surgically explanted stenotic aortic valves, suggesting an infiltration of atherogenic apoB‐containing lipoproteins into the valve leaflets 32. Interestingly, apoA‐I was also found in explanted stenotic aortic valves 33. The latter finding could be related to the modification of apoA‐I by proteins such as matrix metalloproteinases, increasing its affinity to proteoglycans, and altering its reverse cholesterol transport function, leading to its accumulation within tissues 33, 34, 35, 36.…”

The lipid theory in the pathogenesis of calcific aortic stenosis

“…Yet, other evidence suggest that HDL might promote AS. In fact, in explanted stenotic human AV, apolipoprotein A1 of HDL has been found close to calcific nodules and contributes to the production of amyloid proteins which promote the transition of isolated valvular interstitial cells (VICs) toward an osteoblast phenotype [22]. Studies conducted on hypercholesterolemic rabbits showed that infusion of apoA-I mimetic could favorably affect AS progression in terms of valve area and leaflets thickness [23].…”

Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome for Apolipoprotein A-I

“…Westermark et al (19,22,(25)(26)(27)(28)(29), a novel scenario is emerging in which wild-type apoA-I is the main component of amyloid fibrils isolated from, so far, lung nodules (21), knee joints (22), peripheral neural tissues (sciatic nerve) (23), aortic valves (24), aorta atherosclerotic plaques (25,26), and peripheral atherosclerotic plaques (27). Interestingly, in some cases, not only N-terminal fragments but full-length wild-type apoA-I was found in the amyloid fibrils extracted from clinical samples (23).…”