{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:27:16Z","timestamp":1790141236427,"version":"4.0.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      Calcium channel blockers, such as dihydropyridines, are commonly used to inhibit enhanced activity of vascular Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channels in hypertension. However, patients who are insensitive to such treatments develop calcium channel blocker-resistant hypertension. The function of Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channel is diversified by alternative splicing, and the splicing factor PTBP (polypyrimidine tract-binding protein) 1 influences the utilization of mutually exclusive exon 8\/8a of the Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channel during neuronal development. Nevertheless, whether and how PTBP1 makes a role in the calcium channel blocker sensitivity of vascular Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channels, and calcium channel blocker-induced vasodilation remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      We detected high expression of PTBP1 and, inversely, low expression of exon 8a in Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channels (Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2\n                      <jats:sub>E8a<\/jats:sub>\n                      ) in rat arteries. In contrast, the opposite expression patterns were observed in brain and heart tissues. In comparison to normotensive rats, the expressions of PTBP1 and Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2\n                      <jats:sub>E8a<\/jats:sub>\n                      channels were dysregulated in mesenteric arteries of hypertensive rats. Notably, PTBP1 expression was significantly downregulated, and Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2\n                      <jats:sub>E8a<\/jats:sub>\n                      channels were aberrantly increased in dihydropyridine-resistant arteries compared with dihydropyridine-sensitive arteries of rats and human. In rat vascular smooth muscle cells, PTBP1 knockdown resulted in shifting of Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 exon 8 to 8a. Using patch-clamp recordings, we demonstrated a concomitant reduction of sensitivity of Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channels to nifedipine, due to the higher expression of Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2\n                      <jats:sub>E8a<\/jats:sub>\n                      isoform. In vascular myography experiments, small interfering RNA-mediated knockdown of PTBP1 attenuated nifedipine-induced vasodilation of rat mesenteric arteries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      PTBP1 finely modulates the sensitivities of Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channels to dihydropyridine by shifting the utilization of exon 8\/8a and resulting in changes of responses in dihydropyridine-induced vasodilation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.120.315010","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T05:03:05Z","timestamp":1597294985000},"page":"2440-2453","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Aberrant Exon 8\/8a Splicing by Downregulated PTBP (Polypyrimidine Tract-Binding Protein) 1 Increases Ca\n                    <sub>V<\/sub>\n                    1.2 Dihydropyridine Resistance to Attenuate Vasodilation"],"prefix":"10.1161","volume":"40","author":[{"given":"Jianzhen","family":"Lei","sequence":"first","affiliation":[{"name":"Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Jiangsu, China (J.L., M.S., Y.Z., J.F., G.Z., 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