| First Author | Henninger DD | Year | 1997 |
| Journal | Circ Res | Volume | 81 |
| Issue | 2 | Pages | 274-81 |
| PubMed ID | 9242189 | Mgi Jnum | J:42527 |
| Mgi Id | MGI:1095951 | Doi | 10.1161/01.res.81.2.274 |
| Citation | Henninger DD, et al. (1997) Low-density lipoprotein receptor knockout mice exhibit exaggerated microvascular responses to inflammatory stimuli. Circ Res 81(2):274-81 |
| abstractText | The objective of this study was to determine whether genetically induced hypercholesterolemia affects leukocyte-endothelial cell interactions in postcapillary venules of the mouse cremaster muscle. Leukocyte adhesion, emigration, and other microvascular parameters were assessed in venules of normal (wild-type) and low-density lipoprotein receptor-deficient (LDLr-/-) mice maintained on either normal rodent chow or on a high cholesterol diet (HCD). Measurements were obtained under control conditions and after administration of either leukotriene B4 (LTB4), platelet-activating factor (PAF), or tumor necrosis factor-alpha (TNF-alpha). Elevated numbers of adherent and emigrated leukocytes were observed in venules of LDLr-/- (compared with wild-type) mice on HCD, both under baseline conditions and after exposure to either LTB4, PAF, or TNF-alpha. Plasma TNF-alpha levels were also elevated in LDLr-/- versus wild-type mice. Administration of blocking monoclonal antibodies demonstrated that intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1, mediates the exaggerated leukocyte-endothelial cell adhesion observed in LDLr-/- mice. The results of these studies indicate that chronic hypercholesterolemia predisposes the microvasculature to intense leukocyte-endothelial cell adhesion in response to different inflammatory stimuli. |
