{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:30:31Z","timestamp":1779928231552,"version":"3.53.1"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["grants 299200, 275614, and 316664"],"award-info":[{"award-number":["grants 299200, 275614, and 316664"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Finnish foundation of cardiovascular research"},{"DOI":"10.13039\/100015736","name":"Folkh\u00e4lsanin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010113","name":"Wilhelm och Else Stockmanns Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010113","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Liv och H\u00e4lsa Society"},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","award":["NNFOC0013659"],"award-info":[{"award-number":["NNFOC0013659"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010135","name":"Finska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010119","name":"Stiftelsen Dorothea Olivia, Karl Walter och Jarl Walter Perkl\u00e9ns Minne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010119","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish foundation of cardiovascular research"},{"name":"Helsinki university hospital research funds"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Vascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (DR). Previously, we have reported an association between mutations in a gene coding for the L-type calcium channel subunit, VEGF and DR. L-type calcium channel blockers (LTCCBs) have been widely used as antihypertensive medication (AHM), but their association with VEGF and DR is still unclear. Therefore, we explored the effect of LTCCBs compared to other AHMs on VEGF concentrations in retinal cells and human serum. Furthermore, we evaluated the association between the use of LTCCBs and the risk of severe diabetic eye disease (SDED).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Research design and methods<\/jats:title>\n                    <jats:p>M\u00fcller cells (MIO-M1) were cultured as per recommended protocol and treated with LTCCBs and other AHMs. VEGF secreted from cells were collected at 24 hours intervals. In an interventional study, 39 individuals received LTCCBs or other AHM for four weeks with a four-week wash-out placebo period between treatments. VEGF was measured during the medication and placebo periods. Finally, we evaluated the risk of SDED associated with LTCCB usage in 192 individuals from the FinnDiane Study in an observational setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the cell cultures, the medium VEGF concentration increased time-dependently after amlodipine (P&lt;0.01) treatment, but not after losartan (P&gt;0.01), or lisinopril (P&gt;0.01). Amlodipine, but no other AHM, increased the serum VEGF concentration (P&lt;0.05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LTCCB increases VEGF concentrations in retinal cells and human serum. However, the usage of LTCCBs does not appear to be associated with SDED in adults with type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0284364","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T13:47:45Z","timestamp":1681393665000},"page":"e0284364","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["L-type calcium channel blocker increases VEGF concentrations in retinal cells and human 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B.","family":"Parente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valma","family":"Harjutsalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raija","family":"Lithovius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinnakaruppan","family":"Mathavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Lehto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo P.","family":"Hiltunen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo 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