開催日時： 平成１８年３月２０日（月） １６：００～１７：００
講 師： Dr. Shu-Wha Lin
所 属： Professor&s_comma; Transgenic Mouse Models Core Facility&s_comma; College of Medicine&s_comma; National Taiwan University
演 題： Mouse Models for platelet and vascular function
概 要： Platelets are important for blood clot formation by aggregating themselves and by secretion of vasoconstrictive compounds such as thromboxane A2 (TxA2). Uncontrolled platelet aggregation is highly associated with vascular disfunctions. We have successfully generated TxA2 knockout (KO) mice which allow us to dissect the role of TxA2 and platelets in atherosclerogenesis and in vascular diseases. We have bred the mice into ApoE-/- background. TxA2ApoE double KO mice are less susceptible than TxA2 null mice to high-cholesterol diet induced vessel lesion. The impact of TxA2 on the proliferative response in atherosclerotic cardiovascular conditions
was evaluated in the carotid vascular ligation model. The experiments showed that the TxA2 KO mice are exempted from neointima formation upon vascular occlusions. The intima/media ratio (I/M) of the occluded vessel of wild-type mice is 2-times higher than that of the occluded vessel of TxA2 KO mice.
This effect is also estrogen dependent. When the mice were subjected to injury at the femoral artery&s_comma; a model mimicking balloon angioplasty in human&s_comma; they showed similar phenotypes as the receptor TP KO mice that had decreased I/M compared to wild-type mice. Although TxA2 mice showed similar extent of re-endothelialization&s_comma; the COX-2 and MMP-9 expressions were down regulated in TxA2 KO mice. These results indicated that TxA2 plays an important role in atherosclerosis and cardiovascular injury. The effect of TxA2 might not be explained by PGH2 or other shunted metabolites that function through TP. Continuing on this line of work to investigate whether combination of TxA2 and TP antagonists has better therapeutic efficacy in experimental animal model for cardiovascular diseases&s_comma; we have generated TxA2/TP double KO mice and used them in related studies and the research is ongoing.