Thrombosis is a major component of cardiovascular disease. Thrombosis occurs in both arteries and veins. Arteries and veins differ biochemically, compositionally, structurally, and hemodynamically. Also, arterial thrombi are platelet rich and red cell poor. Thrombi in veins are red cell and fibrin rich and platelet poor. Stable thrombus formation in the carotid artery (CA) in response to FeCl3-induced injury has been characterized extensively, and is dependent on glycoprotein Ib (GPIb). Stable thrombus formation in veins, not venules has not been characterized extensively. Here, we compare the requirements for stable thrombus formation in response to FeCl3-induced injury in mouse CA with those for stable thrombus formation induced by FeCl3 in mouse inferior vena cava (IVC). The structural differences between the CA and the IVC preclude equivalent preparation of the two types of vessels. The tissue surrounding the CA can be separated from the vessel without obviously damaging it, allowing easy access by the FeCl3. The tissue surrounding the IVC cannot be readily separated from the vessel without damaging it. So, the vessel preparations are not equivalent. Stable thrombus formation was monitored using a laser Doppler system. Stable thrombus formation in C57BL/6J mice occurred in the CA in about 5 minutes in response to injury induced by exposure to FeCl3 (10%, 3 min) and was dependent on GPIb. Strikingly, stable thrombus formation in the IVC did not occur reproducibly in response to 10% FeCl3 even following exposure for 10 minutes. Exposure to a 20% FeCl3 solution for 10 minutes was required to reproducibly elicit stable thrombus formation in the IVC of control mice; stable thrombi formed in about 28 minutes. Dependence of stable thrombus formation in the IVC on GPIb in response to FeCl3 induced injury was characterized using genetically altered mice. GPIb−/− mice did not support stable thrombus formation (20%, 10 min). Because the low platelet count and/or the large platelet size of the platelets in these Bernard-Soulier syndrome like mice may have affected thrombus formation, mice lacking the extracellular domain of GPIb, but possessing the transmembrane and cytoplasmic domains of GPIb were tested in this system. These mice designated IL-4R, have platelets of normal size and number but lack murine GPIb. They express modified human GPIb composed of the transmembrane and cytoplasmic domains of human GPIb and the extracellular domain of interleukin 4 receptor (IL-4R) instead of the extracellular domain of human GPIb. Both mouse strains, GPIb−/− and the IL-4R, are present in a C57BL/6J background as a result of 10 generation backcrossing to C57BL/6J animals. Stable thrombi did not form in these mice in response to FeCl3. These data demonstrate that as in the CA, stable thrombus formation in the IVC requires GPIb. Surprisingly, these results conflict with those reported for FeCl3-induced stable thrombus formation in mesenteric venules which is GPIb-independent, but von Willebrand factor-dependent.
Disclosure: No relevant conflicts of interest to declare.