{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:38:14Z","timestamp":1789763894255,"version":"4.0.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1\u2010AAs) extensively exist in patients with hypertensive diseases and have been demonstrated to play crucial roles in the pathophysiological process of vascular remodeling. However, the treatment options are limited. The large\u2010conductance calcium\u2010activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture. We have previously observed that AT1\u2010AAs have an inhibitory effect on BK channels. However, whether BK channel dysfunction is involved in AT1\u2010AAs\u2010induced vascular remodeling and the therapeutic effect of BK channel opener is unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In our study, mesenteric arteries from AT1\u2010AAs\u2010positive rats exhibited increased wall thickness, narrowing of the arteriolar lumen, and increased collagen accumulation. Patch clamp test results showed that the voltage sensitivity of BK channel declined in mesenteric arteriolar smooth muscle cells from AT1\u2010AAs\u2010positive rats. Experiments with freshly isolated mesenteric arteriolar smooth muscle cells showed that AT1\u2010AAs reduced the opening probability, open levels, open dwell time, and calcium sensitivity of BK channel. Experiments with HEK293T cells transfected with GFP\u2010ZERO\u2010BK \u03b1\u2010subunit plasmids suggested a BK channel \u03b1\u2010subunit\u2010dependent mechanism. BK channel \u03b1\u2010subunit deficient, namely\n              <jats:italic>KCNMA1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              rats showed a phenotype of mesenteric artery remodeling. The administration of NS1619, a specific BK channel opener targeting the \u03b1\u2010subunit, reversed the phenotypic transition and migration induced by AT1\u2010AAs in cultured mesenteric arteriolar smooth muscle cells. Finally, perfusion of NS1619 significantly relieved the pathological effects induced by AT1\u2010AAs in vivo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In summary, we provide compelling evidence that BK channel \u03b1\u2010subunit dysfunction mediates AT1\u2010AAs\u2010induced mesenteric artery remodeling. Preservation of BK channel activity may serve as a potential strategy for the treatment of AT1\u2010AAs\u2010induced maladaptive resistance artery remodeling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.024046","type":"journal-article","created":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T11:01:12Z","timestamp":1644663672000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Large\u2010Conductance Calcium\u2010Activated Potassium Channel Opener, NS1619, Protects Against Mesenteric Artery Remodeling Induced by Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor"],"prefix":"10.1161","volume":"11","author":[{"given":"Meili","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medical Sciences Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular 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