Colocalization of cholesterol and hydroxyapatite in human atherosclerotic lesions

Abstract

Cholesterol and calcium phosphate, the latter in the form of hydroxyapatite, accumulate in atherosclerotic lesions. In this report, we demonstrate that these organic and inorganic constituents of lesions can accumulate together, closely associated in crystal agglomerates. Using the fluorescent cholesterol probe, filipin, we identified unesterified cholesterol that was associated with calcium granules in tissue sections of lesions. We also have shown that small crystallites of cholesterol can associate with preformed hydroxyapatite crystals in vitro. Scanning electron microscopy coupled with energy-dispersive X-ray analysis demonstrated the physical association of many small crystallites of cholesterol with larger crystals of hydroxyapatite. These small crystallites of cholesterol associated with hydroxyapatite stained with filipin. This contrasted with the lack of filipin staining of unassociated larger cholesterol crystals or hydroxyapatite alone. How cholesterol and calcium come to be closely associated in crystal agglomerates within atherosclerotic lesions remains to be determined.

Lipids in biocalcification: contrasts and similarities between intimal and medial vascular calcification and bone by NMR

“…Cholesteryl esters are nearly always associated with atherosclerosis, but what their involvement is in the calcifi cation process is still a matter of considerable debate. Crystallites of cholesterol are found in close proximity to apatitic mineral in atherosclerotic plaques ( 11 ), and in vitro, apatitic crystals are found to grow from cholesterol crystal surfaces ( 12 ), prompting suggestions of a possible templating role. Conversely, hydroxyapatite seed crystals added to phosphatidyl/cholesterol liposomes caused the liposomes to aggregate, suggesting that the lipid role may be much more complex than simple templating.…”

Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis

“…Increased cholesterol delivery, via Lp(a), to the valve leaflets can lead to cholesterol microcrystals which act as nidi for calcification (44). Lp(a), via OxPLs, is also a source of oxidative stress, remains one of the few agents that is currently available that lowers Lp(a) in a dose-dependent fashion.…”

Effect of Lipid Modification on Progression of Coronary Calcification

“…It has been postulated that vesicles, derived from apoptotic foam and smooth muscle cell debris and contained within extracellular matrix, may also serve as the sites of small calcium deposits. A very close spatial association between cholesterol deposits and hydroxyapatite also has been demonstrated (5). The exact mechanism and process of calcification within the arterial wall are not yet completely understood.…”