{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:00:05Z","timestamp":1790312405697,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vascular smooth muscle cells (VSMCs) exhibit heterogeneous responses to mechanical stretch stress (SS), with some undergoing apoptosis and others proliferating. The mechanisms underlying this differential fate decision remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated whether SS-induced heterogeneity in F-actin expression dictates distinct mitochondrial reactive oxygen species (ROS) responses, leading to different VSMC fates, and evaluated the therapeutic potential of the berberine (BBR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>VSMCs were subjected to SS. F-actin heterogeneity was characterized, and mitochondrial ROS (mtROS), proliferation, and apoptosis were assessed. The involvement of the PKC\u03b1\/PDI\/Drp1 signaling axis was examined using pharmacological inhibitors and BBR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SS induced heterogeneous mtROS production in VSMCs with varying F-actin levels. This differential ROS signaling concurrently activated the pro-proliferative mTOR\/p70 pathway and the pro-apoptotic caspase-9\/3 cascade via the PKC\u03b1\/PDI\/Drp1 axis. Importantly, BBR treatment effectively attenuated both SS-induced proliferation and apoptosis by suppressing PKC\u03b1 activation and subsequent mitochondrial signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings reveal that F-actin heterogeneity determines VSMC fate under SS by driving distinct mitochondrial ROS responses. BBR, by counteracting these ROS-dependent pathways, emerges as a promising therapeutic strategy for managing stretch-related vascular pathologies, such as hypertension-induced atherosclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1921727","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:27:26Z","timestamp":1790310446000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine suppresses mechanical stretch-induced apoptosis and proliferation in vascular smooth muscle cells via ROS\/PDI\/Drp1 signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Ning","family":"Lin","sequence":"first","affiliation":[{"name":"Key laboratory of Functional and Clinical Translational Medicine, Fujian province, Xiamen Medical College","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongshan People\u2019s Hospital","place":["Zhongshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Cai","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhongshan School of Medicine, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaolian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongshan People\u2019s Hospital","place":["Zhongshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Zhongshan People\u2019s Hospital","place":["Zhongshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Zhongshan People\u2019s Hospital","place":["Zhongshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41392-023-01560-y","article-title":"NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice","volume":"8","author":"Cheng","year":"2023","journal-title":"Signal Transduct. 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