| First Author | Braun H | Year | 2024 |
| Journal | Biochem Pharmacol | Volume | 219 |
| Pages | 115916 | PubMed ID | 37979705 |
| Mgi Jnum | J:343643 | Mgi Id | MGI:7565031 |
| Doi | 10.1016/j.bcp.2023.115916 | Citation | Braun H, et al. (2023) Deletion of vascular thromboxane A(2) receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice. Biochem Pharmacol 219:115916 |
| abstractText | The thromboxane A(2) receptor (TP) has been shown to play a role in angiotensin II (Ang II)-mediated hypertension and pathological vascular remodeling. To assess the impact of vascular TP on Ang II-induced hypertension, atherogenesis, and pathological aortic alterations, i.e. aneurysms, we analysed Western-type diet-fed and Ang II-infused TP(VSMC KO)/Ldlr KO, TP(EC KO)/Ldlr KO mice and their respective wild-type littermates (TP(WT)/Ldlr KO). These analyses showed that neither EC- nor VSMC-specific deletion of the TP significantly affected basal or Ang II-induced blood pressure or aortic atherosclerotic lesion area. In contrast, VSMC-specific TP deletion abolished and EC-specific TP deletion surprisingly reduced the ex vivo reactivity of aortic rings to the TP agonist U-46619, whereas VSMC-specific TP knockout also diminished the ex vivo response of aortic rings to Ang II. Furthermore, despite similar systemic blood pressure, there was a trend towards less atherogenesis in the aortic arch and a trend towards fewer pathological aortic alterations in Ang II-treated female TP(VSMC KO)/Ldlr KO mice. Survival was impaired in male mice after Ang II infusion and tended to be higher in TP(VSMC KO)/Ldlr KO mice than in TP(WT)/Ldlr KO littermates. Thus, our data may suggest a deleterious role of the TP expressed in VSMC in the pathogenesis of Ang II-induced aortic atherosclerosis in female mice, and a surprising role of the endothelial TP in TP-mediated aortic contraction. However, future studies are needed to substantiate and further elucidate the role of the vascular TP in the pathogenesis of Ang II-induced hypertension, aortic atherosclerosis and aneurysm formation. |
