| Abstrakt: |
Serotonin (5-HT) has been implicated in cerebral aneurysm rupture, but it is unclear if 5-HT plays a role in aortic aneurysm development and rupture, despite well-known contractile effects of 5-HT through aortic 5-HT receptors. Abdominal aortic aneurysms (AAAs) induced by angiotensin II (AngII) infusion to mice exhibit periaortic inflammation and are prone to rupture. Periaortic fat (PAF), a potential source of 5-HT through tryptophan hydroxylase 1 (Tph1), has been implicated in AAA development. We quantified mRNA abundance of 5-HT receptors (Htr1b, Htr2a, Htr2b, Htr3a, Htr7)and Tph1in thoracic and abdominal aortas and surrounding PAF. Compared to other 5-HT receptors, we detected high levels of serotonin 3 receptor type a (Htr3a)mRNA in abdominal aortas and abdominal PAF. Tph1mRNA and 5-HT immunostaining were detected in aortas and PAF, with 5-HT levels higher in abdominal than thoracic PAF, and higher in epididymal white than interscapular brown fat. AngII infusion facilitated evoked [3]5-HT release from thoracic PAF and modestly reduced 5-HT levels in thoracic PAF and brown fat. Based on a high level of Htr3amRNA in abdominal aortas and PAF, we investigated the development of AngII-induced AAAs when 5-HT3R were pharmacologically antagonized with Tropisetron (Tropi). Tropi abrogated abdominal aortic lumen diameters, aneurysm (DTA, AAA) incidence, maximal AAA diameters and aortic weights of AngII-infused male mice. These findings indicate a novel role for 5-HT3R in AAA development, with a potential clinically relevant contribution for PAF as a local source of 5-HT. |
