Abstract 18172: Nicotine Accelerates the Expansion of Abdominal Aortic Aneurysms via a Matricellular Protein, Periostin
Abdominal aortic aneurysms (AAA) are more closely associated with cigarette smoking than any other tobacco-related disease except lung cancer. Periostin (PN) is a matricellular protein that is induced by mechanostress and regulates organ remodeling. Our previous study has shown that PN was significantly unregulated in early remodeling phase of AAAs and its ablation contributed to reduce AAA growth induced by angiotension ll (Angll). The purpose of the present study was to investigate the effect of nicotine on PN and its potential role 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) for 28 days or nicotine (7.0 mg/kg/min) for 42 days was administrated via osmotic minipumps for 24 >-wk-old male mice. 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 (101.4±7.3 vs 107.6±8.3mmHg, ns).
The BP response to Ang II or nicotine in ApoE/PN-dKO mice was also similar to that in ApoE-KO mice throughout the observation period (data not shown). In Ang II treated mice, the expansion rate of the aortic diameter (AD) was decreased significantly in ApoE/PN-DKO mice (n=10) over ApoE-KO mice (n=12) from day7 to 28day (239.3±43.4% vs 144.4±8.5% at day 28, p<0.05). Moreover the incidence of rupture and hematoma was significantly reduced in ApoE/PN-DKO mice at day 28 (60.0% vs 16.7% at day 28, p<0.05). In nicotine treated mice, the expansion rate of the AD was also diminished in ApoE/PN-DKO mice (n=5) over ApoE-KO mice (n=10) at day 42 (156.1±9.6 vs 113.9±4.0% at day 42, p<0.05). However no rupture or hematoma was observed in this treatment group.
The present study investigated the effect of nicotine on PN and their potential role in progressing AAAs. AngII had more potential induction of AAA rupture than nicotine in ApoE KO mice. Although the mechanism to develop AAA would be partially different between AngII and nicotine, the ablation of PN limited the AAA expansion in both AAA model. Antagonists against PN would lead to new therapeutic targets on a molecular basis to limit AAA progression related to cigarette smoking.
- © 2013 by American Heart Association, Inc.