Journal Article

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

Parente, Erika B., Lehto, Markku, Mutter, Stefan, Hiltunen, Timo P., Kumar, Anmol, Kontula, Kimmo K., Lithovius, Raija, Groop, Per-Henrik, Mathavan, Sinnakaruppan, Harjutsalo, Valma

2023

Overview

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). 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Amlodipine - pharmacology / Antihypertensive Agents - therapeutic use / Antihypertensives / Biology and Life Sciences / Calcium / Calcium channel blockers / Calcium Channel Blockers - pharmacology / Calcium Channel Blockers - therapeutic use / Calcium channels / Calcium channels (L-type) / Cell culture / Comparative analysis / Complications and side effects / Diabetes / Diabetes mellitus / Diabetes mellitus (insulin dependent) / Diabetic retinopathy / Diabetic Retinopathy - metabolism / Diagnosis / Endocrine system / Evaluation / Eye diseases / Genetic aspects / Growth factors / Health aspects / Health risks / Hospitals / Humans / Hydrochlorothiazide / Hypertension / Medical research / Medicine and health sciences / Medicine, Experimental / Mueller cells / Mutation / Observational studies / Physical Sciences / Placebos / Research and Analysis Methods / Research design / Retina / Retinal cells / Retinopathy / Risk / Type 1 diabetes / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - metabolism