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Although numerous studies have been conducted on them separately, their communication and interaction remain unclear. We used porcine aortic valves to isolate valve interstitial cells (VICs). VICs were induced to differentiate into myofibroblasts by transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21). After successful activation was determined, the myofibroblast\u2010conditioned medium (CM) was collected and used to act on RAW264.7, a macrophage cell line. A migration and adhesion assay estimated the recruitment capability of myofibroblasts on macrophages. We used flow cytometry, quantitative polymerase chain reaction (qPCR), and Western blot analysis to investigate myofibroblasts' polarity promotion function in macrophages. Finally, we used macrophage\u2010CM on VICs to explore the differentiation induction function of polarized macrophages. Myofibroblast marker alpha\u2010smooth muscle actin and M2 macrophage marker CD163 were detected as upregulated in CAVD patients, and their expression has a certain correlation. The Smad3\/HA\/CD44 axis activated the differentiation of myofibroblasts by Western blot. The myofibroblast\u2010CM can promote chemotaxis and adhesion of macrophages through protein kinase B\/chemokine (C\u2013C motif) ligand5 and Smad3\/HA\/CD44, respectively. Hyaluronic acid (HA) inside the myofibroblast\u2010CM stimulates macrophages to polarize into M2 macrophages. In turn, M2 macrophage\u2010CM has the promotive ability to activate myofibroblasts but fails to induce the osteoblast differentiation of VICs directly. The crosstalk between myofibroblasts and macrophages causes the excessive activation of myofibroblasts. This positive feedback loop may play a vital role in CAVD progression.<\/jats:p>","DOI":"10.1002\/cbin.11980","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T18:25:25Z","timestamp":1671647125000},"page":"754-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Crosstalk between myofibroblasts and macrophages: A regulative factor of valvular fibrosis in calcific aortic valve disease"],"prefix":"10.1002","volume":"47","author":[{"given":"Lujia","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1649-8520","authenticated-orcid":false,"given":"Lin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Changhai Hospital Second Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"Celada L. 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