{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:33:04Z","timestamp":1792153984219,"version":"4.4.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (M\u03c6s) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2M\u03c6s, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1M\u03c6s), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2M\u03c6s and improved myocardial fibrosis, but interestingly, both M1M\u03c6s and M2M\u03c6s were increased in the peritoneal cavity of SHRs, the number of M2M\u03c6s remained lower than M1M\u03c6s. <jats:italic>In vitro<\/jats:italic>, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1M\u03c6s. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1M\u03c6s and increasing M2M\u03c6s.<\/jats:p>","DOI":"10.3389\/ebm.2024.10112","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T04:11:30Z","timestamp":1712290290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Calcium-sensing receptor-mediated macrophage polarization improves myocardial remodeling in spontaneously hypertensive rats"],"prefix":"10.3389","volume":"249","author":[{"given":"Jiaqi","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"61","DOI":"10.2147\/jir.s148911","article-title":"Inflammation and oxidative stress markers in diabetes and hypertension","volume":"11","author":"Pouvreau","year":"2018","journal-title":"J Inflamm Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.semcdb.2015.11.006","article-title":"Calcium-sensing receptor, proinflammatory cytokines and calcium homeostasis","volume":"49","author":"Hendy","year":"2016","journal-title":"Semin Cel Dev Biol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.2174\/1381612828666220922112412","article-title":"Innate immune response in hypertension","volume":"28","author":"De Sanctis","year":"2022","journal-title":"Curr Pharm Des"},{"key":"B4","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1172\/jci59643","article-title":"Macrophage plasticity and polarization: in vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J Clin Invest"},{"key":"B5","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1161\/circresaha.111.300484","article-title":"Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts","volume":"112","author":"Jung","year":"2013","journal-title":"Circ Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/s41577-018-0065-8","article-title":"Cardioimmunology: the immune system in cardiac homeostasis and disease","volume":"18","author":"Swirski","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.pharmthera.2018.02.011","article-title":"Inflammasome biology, molecular pathology and therapeutic implications","volume":"187","author":"Awad","year":"2018","journal-title":"Pharmacol Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/s0022-2143(97)90178-5","article-title":"Increased serum levels of interleukin-1\u03b2 in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients?","volume":"129","author":"Dalekos","year":"1997","journal-title":"J Lab Clin Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbadis.2017.10.001","article-title":"The SGK1 inhibitor EMD638683, prevents Angiotensin II-induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation","volume":"1864","author":"Gan","year":"2018","journal-title":"Biochim Biophys Acta (Bba) - 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