Abstract 15123: Periostin Regulates Aortic Rupture and Remodeling in Angiotensin II Induced Abdominal Aortic Aneurysm
Abdominal aortic aneurysm (AAA) has complex hemodynamics which leads various mechanical stresses in aortic wall. Periostin (PN) is a matricellular protein that is induced by mechanostress and regulates organ remodeling. Our previous genome transcriptional profiling of the murine angiotensin II (Ang II) induced AAA have shown 3.5-fold up-regulation of PN in AAA in early remodeling phase over saline-control sample. Moreover we also found it was highly expressed in human AAA samples. The purpose of the present study was to investigate the potential role of PN in AAA disease progression.
PN-knockout (KO) mice were originally generated in our lab and crossed with ApoE-KO mice to establish ApoE/PN-double knockout (dKO) mice. Ang II (1.0 mg/kg/min) was infused into 24>-wk-old male mice for 28 days via osmotic minipumps. Growth of AAAs was serially monitored by ultrasound imaging. The systolic blood pressure (BP) measured by tail cuff method was equivalent between ApoE-KO and ApoE/PN-dKO mice at baseline (100.1±2.4 vs 99.5±5.1mmHg, ns). No histological difference was observed in aortic structure between them. The BP response to Ang II in ApoE/PN-dKO mice was also similar to that in ApoE-KO mice throughout the observation period (data not shown). Surprisingly, no ApoE/PN-dKO (and four in ApoE-KO mice) died due to rupture of AAAs. Also the incidence of rupture and hematoma was significantly reduced in ApoE/PN-dKO mice at day 28 (figure). The expansion rate of the aortic diameter was decreased in ApoE/PN-dKO mice over ApoE-KO mice at 7days (147.9±3.9 vs. 180.0±6.5%, p<0.05). However the tendency was diminished at day 28. (189.3±21.6 vs. 214.3±29.0%, ns)
The present study investigated the potential role of PN in progressing AAAs. PN was significantly unregulated in early remodeling phase of AAAs and its ablation contributed to reduce AAA growth. Antagonists against PN will potentially lead to new therapeutic targets on a molecular basis to limit AAA disease progression.
- © 2012 by American Heart Association, Inc.