Differential accumulation of intimal monocyte-macrophages relative to lipoproteins and lipofuscin corresponds to hemodynamic forces on cardiac valves in mice.
We have studied the distribution of monocyte-macrophages, lipids, and lipoproteins in sections of aorta and aortic valves from mice fed an atherogenic diet. By immunocytochemical analysis with Mac-1 and F4/80 antibodies, apolipoprotein B antibody, and oil red O staining, three discrete regions were identified: 1) the aortic wall of the sinus of Valsalva, which contained deposits of lipid that colocalized with lipoproteins and monocyte-macrophages; 2) the sides of the aortic valve leaflets facing the ventricle, which did not contain lipids or lipoproteins but which were lined with macrophages that colocalized with lipofuscin; and 3) the sides of the leaflets facing the aorta, which did not contain lipids, lipoproteins, monocyte-macrophages, or lipofuscin deposits. This pattern of distribution resembles the expected distribution of mechanical forces, especially those of systolic blood flow, which in the three areas are predominantly 1) low-shear disturbed flow, 2) high-shear laminar flow, and 3) low-shear laminar flow, respectively. These findings suggest that lesions in the mouse closely resemble early atherosclerotic lesions in humans and other primates with respect to monocyte-macrophage and lipoprotein accumulation. The results also strikingly demonstrate that the accumulation of monocyte-macrophages and lipoproteins can occur independently, with spatial differences corresponding to the distribution of hemodynamic forces.
Mehrabian
M
M
Cardiology Division, UCLA School of Medicine 90024-1679.
Demer
L L
LL
Lusis
A J
AJ
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004041:Dietary Fats; D005260:Female; D006439:Hemodynamics; D007124:Immunoenzyme Techniques; D008062:Lipofuscin / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology*; D012850:Sinus of Valsalva / Q000378:metabolism
D001055:Apolipoproteins B; D004041:Dietary Fats; D008062:Lipofuscin; D008074:Lipoproteins