| First Author | Nishida N | Year | 2020 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 40 |
| Issue | 1 | Pages | 189-205 |
| PubMed ID | 31694392 | Mgi Jnum | J:289954 |
| Mgi Id | MGI:6435242 | Doi | 10.1161/ATVBAHA.119.313336 |
| Citation | Nishida N, et al. (2020) High Salt Intake Worsens Aortic Dissection in Mice: Involvement of IL (Interleukin)-17A-Dependent ECM (Extracellular Matrix) Metabolism. Arterioscler Thromb Vasc Biol 40(1):189-205 |
| abstractText | OBJECTIVE: Aortic dissection (AD) is a fatal disease that occurs suddenly without preceding clinical signs or symptoms. Although high salt intake is a proposed risk factor for cardiovascular diseases, the relationship between AD and high salt intake has not been clarified. We examined the effect of high-salt challenge on a mouse AD model. Approach and Results: AD was induced in male mice by continuous infusion of beta-aminopropionitrile and Ang II (angiotensin II). High-salt challenge exacerbated aortic wall destruction in AD. Deletion of Il17a (IL-17KO [IL (interleukin)-17A knockout]) did not affect the AD phenotype at baseline, but it abolished the high salt-induced worsening of the aortic destruction. Unexpectedly, aortas of IL-17KO mice exhibited global changes in ECM (extracellular matrix)-related genes without alteration of proinflammatory genes, altered architecture of collagen fibers, and reduced stiffness before AD induction. The aortas of IL-17KO mice were less sensitive to AD-inducing stimuli, as shown by the induction of phenotypic modulation markers SMemb and vimentin, suggesting a reduced stress response. The aortas of IL-17KO mice had a higher population of smooth muscle cells with nuclear-localized phosphorylated Smad2, indicative of TGFbeta (transforming growth factor-beta) signal activation. Consistently, pretreatment of smooth muscle cells in culture with IL-17A blunted the activation of Smad2 by TGFbeta1. CONCLUSIONS: These findings indicate that high salt intake has a worsening effect on AD in the context of high aortic wall stiffness, which is under the control of IL-17A through ECM metabolism. Therefore, salt restriction may represent a low-cost and practical way to reduce AD risk. |
