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

Kumar, A.; Mutter, S.; Parente, E.; Harjutsalo, V.; Lithovius, R.; Mathavan, S.; Forsblom, C.; Lehto, M.; Hiltunen, T. P.; Kontula, K.; Groop, P.-H.

doi:10.1101/2021.12.21.473644

bioRxiv · 10.1101/2021.12.21.473644

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

Kumar, A.·Mutter, S.·Parente, E.·Harjutsalo, V.·Lithovius, R.·Mathavan, S.·Forsblom, C.·Lehto, M.·Hiltunen, T. P.·Kontula, K.·Groop, P.-H.

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Abstract

ObjectiveVascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (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 methodsMuller 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 oberservational setting. ResultsIn the cell cultures, 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 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. ConclusionsLTCCB 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.

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Kumar, A., Mutter, S., Parente, E., Harjutsalo, V., Lithovius, R., Mathavan, S., Forsblom, C., Lehto, M., Hiltunen, T. P., Kontula, K., Groop, P.-H.. 2021-12-23. L-type calcium channel blocker increases VEGF concentrations in retinal cells and human serum. https://doi.org/10.1101/2021.12.21.473644

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