A cytochemical study of the surface properties of aortic and mitral valve endothelium from hypercholesterolemic rabbits.
The luminal surface properties of aortic and mitral valve endothelium in hypercholesterolemic rabbits were examined with the aid of cationic ferritin (CF), ferritin-lectins (FWGA, FRCA, FSBA), and low density lipoprotein-colloidal gold (LDL-Gold) conjugates. Based upon comparative studies with normocholesterolemic rabbit valves, the number of CF and wheat germ agglutinin (FWGA) particles per 100 nm of endothelial surface was found to be reduced in moderate hypercholesterolemia (450 mg/dl). Conversely, the number of Ricinus communis agglutinin (FRCA) and soybean agglutinin (FSBA) conjugates were increased. Quantitation of the CF and FWGA particles demonstrated that the endothelium lining of the valve surfaces (i.e., the arterial surfaces of the aortic cusps, AA, and the ventricular surfaces of the mitral cusps, MV) exposed to more turbulent hemodynamic conditions displayed the greatest densities of particle counts. Cholesterol levels of 400-500 mg/dl produced a loss of characteristic differences in the number of ferritin particles that existed between the two surfaces of a cusp. Especially prominent over the AA and MV surfaces, these changes represented a reduction in the anionic properties of the endothelial glycocalyx. Enzymatic digestion demonstrated the reduction in surface sialic acid residues to be one of the major factors responsible for these early changes at the blood-endothelium interface. More severe hypercholesterolemia (700-900 mg/dl) resulted in even further reductions in the number of ferritin particles over the AA and MV surfaces but enhanced the binding of LDL-Gold. Chondroitinase studies of these specimens demonstrated that the initial loss of sialic acids at moderate serum levels unmasks deeper lying components of the glycocalyx (e.g., sulfated glycosaminoglycans) and augments the attachment of LDL molecules to the endothelial surface. The findings of this study suggest that specific macromolecular changes in the endothelial glycocalyx in diet-induced hypercholesterolemia occur at vascular locales where hemodynamic forces such as eddy formations and blood stagnation impinge against the vascular wall.
D000818:Animals; D001021:Aortic Valve / Q000473:pathology* / Q000648:ultrastructure; D004727:Endothelium / Q000473:pathology; D005293:Ferritins / Q000378:metabolism; D006046:Gold; D006937:Hypercholesterolemia / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008943:Mitral Valve / Q000473:pathology* / Q000648:ultrastructure; D011817:Rabbits
D006046:Gold; D005293:Ferritins