{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:12:05Z","timestamp":1788880325876,"version":"build-2803163510"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n BACKGROUND:<\/jats:title>\n \n Fine-tuning of Ca\n V<\/jats:sub>\n 1.2 calcium channel activity by binding proteins represents a novel mechanism for regulating smooth muscle contraction and blood pressure (BP). This study aimed to elucidate the role of Gal-3 (galectin-3), a newly identified Ca\n V<\/jats:sub>\n 1.2-binding protein, in the pathogenesis of hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n In vitro, ex vivo, and in vivo experiments involving molecular and biochemical assays, in silico prediction, patch-clamp electrophysiologic recordings, immunohistochemistry, pressure myography, and tail-cuff BP measurements were used to evaluate the molecular mechanisms by which Gal-3 binds to and elevates membrane insertion of Ca\n V<\/jats:sub>\n 1.2 channels. The experiments were performed in transfected HEK\u2009293 cells, isolated smooth muscle cells, and arteries from smooth muscle\u2013specific Gal-3 knockout mice and their wild-type littermates; spontaneously hypertensive rats; or human patients. In vivo experiments involving delivery of the blocking iGal3BP (inhibitory galectin-3\u2013binding peptide) into spontaneously hypertensive rats were performed to investigate its effect on BP.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n We identified Gal-3 as a novel binding partner and unexpected positive modulator of the Ca\n V<\/jats:sub>\n 1.2 channel through binding to the intracellular II-III loop. Gal-3 increased total and surface expression, current density, and open probability of Ca\n V<\/jats:sub>\n 1.2 channels. Both Ca\n V<\/jats:sub>\n 1.2 and Gal-3 were upregulated in hypertensive rat aortas and human pulmonary arteries. Conditional deletion of Gal-3 in smooth muscle markedly lowered Ca\n V<\/jats:sub>\n 1.2 protein and BP in mice. With specific binding sites identified within both Gal-3 and the Ca\n V<\/jats:sub>\n 1.2 II-III loop, the peptide iGal3BP, designed to block Ca\n V<\/jats:sub>\n 1.2\u2013Gal-3 interaction, significantly reduced BP in spontaneously hypertensive rats by decreasing Ca\n V<\/jats:sub>\n 1.2 protein expression. Repeated iGal3BP administration resulted in cumulative peptide accumulation in mesenteric arteries and produced a sustained reduction in BP, which demonstrated greater long-lasting antihypertensive efficacy compared with amlodipine and losartan. Administration of iGal3BP in combination with a negative modulatory Gal-1 mimetic peptide that mimics Gal-1\u2013Ca\n V<\/jats:sub>\n 1.2 interaction returned systolic BP to normotensive levels within 4 hours and lowered BP in hypertensive rats in a sustained manner for 35 days.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n \n These results provide strong evidence that Gal-based Ca\n V<\/jats:sub>\n 1.2 channel modulators are novel therapeutic pathways for normalizing BP.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.126.080022","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:00:18Z","timestamp":1781514018000},"page":"819-834","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Galectin-3 Regulates Smooth Muscle Contraction and Blood Pressure by Modulating Ca\n V<\/sub>\n 1.2 Channel Function"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7001-4211","authenticated-orcid":true,"given":"Kelvin Wei Zhern","family":"Loh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5030-0894","authenticated-orcid":true,"given":"Yanruo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3335-7121","authenticated-orcid":true,"given":"Cong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaitanya K.","family":"Jaladanki","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore 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Beijing, China (H.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-7533","authenticated-orcid":true,"given":"Zhenyu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0876-0325","authenticated-orcid":true,"given":"Tuck Wah","family":"Soong","sequence":"additional","affiliation":[{"name":"Integrative Sciences and Engineering Programme, NUS Graduate School, Singapore 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