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Thus, an attractive strategy is to attenuate the myocardial fibrosis to help preserve ventricular function. Here, by analyzing RNA-sequencing databases and comparing the transcript and protein levels of fibrillar collagen in WT and global-knockout mice, we found that slit guidance ligand 3 (SLIT3) was present predominantly in fibrillar collagen\u2013producing cells and that SLIT3 deficiency attenuated collagen production in the heart and other nonneuronal tissues. We then performed transverse aortic constriction or pulmonary artery banding to induce left and right ventricular pressure overload, respectively, in WT and knockout mice. We discovered that SLIT3 deficiency abrogated fibrotic and hypertrophic changes and promoted long-term ventricular function and overall survival in both left and right ventricular pressure overload. Furthermore, we found that SLIT3 stimulated fibroblast activity and fibrillar collagen production, which coincided with the transcription and nuclear localization of the mechanotransducer yes-associated protein 1. These results indicate that SLIT3 is important for regulating fibroblast activity and fibrillar collagen synthesis in an autocrine manner, making it a potential therapeutic target for fibrotic diseases, especially myocardial fibrosis and adverse remodeling induced by persistent afterload elevation.<\/jats:p>","DOI":"10.1172\/jci.insight.136852","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T12:01:04Z","timestamp":1589889664000},"source":"Crossref","is-referenced-by-count":25,"title":["SLIT3 deficiency attenuates pressure overload\u2013induced cardiac fibrosis and remodeling"],"prefix":"10.1172","volume":"5","author":[{"given":"Lianghui","family":"Gong","sequence":"first","affiliation":[{"name":"Section of Pediatric Cardiovascular Surgery, Department of Cardiac Surgery, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA."},{"name":"Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, 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