Abstract 11587: Excessive NaCl Intake Aggravates Aortic Dissection Through IL-17 Pathway
Excessive NaCl intake is an established risk factor of cardiovascular events, although the molecular mechanism has not been fully understood. Aortic dissection (AD) is one of the fatal cardiovascular events, in which proinflammatory response is proposed to be important. In this study, we investigated the effect of excessive NaCl intake on a mouse AD model that was induced by continuous infusion of beta-aminopropionitrile (BAPN), a collagen/elastin crosslink inhibitor, and angiotensin II (AngII). BAPN+AngII caused thoracic and suprarenal AD in most of the mice within 2 weeks. Excessive NaCl intake was achieved by giving 1% NaCl as drinking water (Hi-Na) 1 week prior to and during the BAPN+AngII infusion. The lesion length of AD was significantly longer in Hi-Na group than in normal water group, even though systolic blood pressure or pulse rate showed no significant changes. Because recent studies have demonstrated that excessive NaCl activates TH17/IL-17 pathway that is central to the inflammatory response, we examined the involvement of IL-17 in AD using IL-17 knockout mice (IL17-KO). Deletion of IL-17 gene abolished the exacerbating effect of NaCl on the severity of AD. Transcriptome analysis of aortae before AD onset showed that strong induction of proinflammatory genes and suppression of extracellular matrix (ECM) genes precede the AD development in this model. Although IL-17 is central to inflammatory response in general, alteration of inflammatory response was not prominent in IL17-KO aorta. Instead, genes of ECM was upregulated in IL17-KO at the baseline. With BAPN+AngII and excessive NaCl intake, expression of ECM genes were higher in IL17-KO compared to wild type aorta. Picrosirius red staining showed that the amount of medial collagen fibers, the major ECM to support the physical strength of aorta, was increased in IL17-KO compared to wild type mice without NaCl overload or BAPN+AngII administration. These data uncovered the unexpected role of IL-17 to suppress the ECM deposition in aorta. Because ECM is essential to maintain the physical strength of aortic walls, the increase of ECM would explains why IL17-KO aorta is protected from dissection. NaCl intake and IL-17 may represent important therapeutic targets for AD.
Author Disclosures: N. Nishida: None. H. Aoki: None. S. Ohno: None. M. Nishihara: None. A. Furusho: None. S. Hirakata: None. M. Hayashi: None. S. Ito: None. H. Yasukawa: None. Y. Fukumoto: None.
- © 2015 by American Heart Association, Inc.