|Smith, C wayne|
Submitted to: Microcirculation
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/18/2003
Publication Date: 5/1/2004
Citation: Rumbaut, R.E., Randhawa, J.K., Smith, C.W., Burns, A.R. 2004. Mouse cremaster venules are predisposed to light/dye-induced thrombosis independent of wall shear rate, CD18, ICAM-1, or P-Selectin. Microcirculation. 11:239-247. Interpretive Summary: This paper deals with intravital microscopy as a tool for studying mechanisms of thrombosis in venules. Intravital microscopy is a technique that allows direct visualization of small blood vessels at sites of injury or inflammation. It provides the ability to see the accumulation of white blood cells and platelets in injured vessels. In this study we have found that injury-induced thrombosis does not require adhesion molecules that are necessary for white blood cell attachment to the endothelium, and thrombosis of the small veins occurs more rapidly that thrombosis in small arteries. The events of thrombosis are part of the innate immune response that promotes healing, but may have pathologic significance in some disease states.
Technical Abstract: Objective: Microvascular adhesion of platelets to endothelium occurs in response to various inflammatory stimuli, and in venules is accompanied by adherent leukocytes. In a light/dye injury model, platelet adhesion and thrombi occur preferentially in venules, though the reasons for this predisposition are unknown. The authors sought to determine whether lower wall shear rates or leukocyte' endothelial interactions accounted for preferential platelet thrombi formation in venules relative to arterioles. Methods: A light/dye injury model of microvascular thrombosis was used in the mouse cremaster microcirculation. Results: In wild-type mice (n = 17), the time to form microvascular platelet aggregates was delayed in arterioles by 3.1-fold relative to venules (p < .0001). However, arterioles with spontaneously low wall shear rates, as well as arterioles manipulated to reduce wall shear rate to venous levels, still had delayed thrombosis as compared to venules. Similarly, in animals deficient of CD18, P-selectin, or ICAM-1, the time to form platelet thrombi in arterioles was >3.0-fold higher than in venules. Conclusions: Mouse cremaster venules are predisposed to light/dye-induced microvascular thrombosis. The data suggest that functional differences between arteriolar and venular endothelial cells (independent of wall shear rate and of CD18, P-selectin, and ICAM-1) account for the venular predisposition to thrombosis.