Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL.
Proteoglycans and plasma proteins bound to the endothelial cell glycocalyx are essential for vascular function, but at the same time, they lower capillary tube hematocrit by reducing capillary volume available to flowing blood. Because oxidized low-density lipoproteins (oxLDL) reduce the effective thickness of the glycocalyx (Vink H, Constantinescu AA, and Spaan JAE. Circulation 101: 1500-1502, 2000), we designed the present study to determine whether this is caused by pathological degradation of glycocalyx constituents or increased glycocalyx deformation by elevated shear forces of flowing blood. Capillaries from the right cremaster muscle of 24 hamsters were examined by using intravital microscopy after systemic administration of normal LDL (n = 4), moderate oxLDL (6-h oxidation with CuSO(4), n = 7), severe oxLDL (18-h oxidation, n = 5), and moderate oxLDL plus superoxide dismutase (SOD) and catalase (n = 8). Capillary tube hematocrit increased from 0.16 +/- 0.03 to 0.37 +/- 0.05 and from 0.15 +/- 0.01 to 0.31 +/- 0.03 after moderate oxLDL and severe oxLDL, respectively. These changes were paralleled by increases in red blood cell flux from 8.7 +/- 1.9 to 13.8 +/- 3 and from 10.7 +/- 2.1 to 16.3 +/- 3.2 cells/s after moderate oxLDL and severe oxLDL, respectively, in the absence of changes in anatomic capillary diameter. Red blood cell velocity, as a measure for the shear forces on the glycocalyx, was not affected by oxLDL, whereas tissue pretreatment with SOD and catalase completely abolished the effects of oxLDL on glycocalyx thickness, capillary hematocrit, and red blood cell flux. We conclude that elevation of capillary tube hematocrit by oxLDL reflects degradation of the endothelial glycocalyx by oxygen-derived free radicals.
Constantinescu
A A
AA
Department of Medical Physics, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
Vink
H
H
Spaan
J A
JA
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D019276:Glycocalyx / Q000378:metabolism* / Q000473:pathology*; D006400:Hematocrit; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000098:blood supply; D017382:Reactive Oxygen Species / Q000378:metabolism
D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein