L-type calcium channel blocker increases VEGF concentrations in retinal cells and human serum

PLoS One. 2023 Apr 13;18(4):e0284364. doi: 10.1371/journal.pone.0284364. eCollection 2023.

Abstract

Objective: 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).

Research design and methods: Müller 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.

Results: In the cell cultures, the medium VEGF concentration increased time-dependently after amlodipine (P<0.01) treatment, but not after losartan (P>0.01), or lisinopril (P>0.01). Amlodipine, but no other AHM, increased the serum VEGF concentration (P<0.05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study.

Conclusions: 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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amlodipine / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Diabetic Retinopathy* / metabolism
  • Humans
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Calcium Channel Blockers
  • Antihypertensive Agents
  • Amlodipine

Grants and funding

The GENRES Study was supported by The Sigrid Juselius Foundation and The Finnish Foundation for Cardiovascular Research.The FinnDiane study was supported by grants from Folkhälsan Research Foundation; Wilhelm och Else Stockmanns Stiftelse; Academy of Finland (grants 299200, 275614, and 316664); Liv och Hälsa Society; Novo Nordisk Foundation (grant NNFOC0013659); Medical Society of Finland (Finska Läkaresällskapet); Dorothea Olivia, Karl Walter and Jarl Walter Perklen Foundation; Päivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; Finnish Foundation for Cardiovascular Research; and Helsinki University Hospital Research Funds (EVO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.