# microRNA‐210 in red blood cells differentially regulates vascular endothelial function between type 1 and type 2 diabetes

## TL;DR

Red blood cells from type 2 diabetes patients reduce endothelial function due to low microRNA-210, unlike type 1 diabetes, suggesting a new therapeutic target.

## Contribution

This study identifies microRNA-210 in red blood cells as a novel regulator of vascular health differing between type 1 and type 2 diabetes.

## Key findings

- T2D red blood cells impair endothelial function and nitric oxide production compared to healthy controls.
- microRNA-210 levels are reduced in T2D red blood cells but not in T1D.
- Inhibiting microRNA-210 in T1D red blood cells impairs endothelial relaxation and increases oxidative stress markers.

## Abstract

Red blood cells from individuals with type 2 diabetes (T2D RBC) induce endothelial dysfunction due to reduced RBC microRNA‐210 levels, whereas T1D RBCs do not. We hypothesize that microR‐210 plays a protective role explaining this difference. Both male and female adults with T1D and T2D matched for glycated hemoglobin, alongside age‐ and sex‐matched healthy controls, were studied. microR‐210 levels were measured by qPCR. Endothelium‐dependent relaxation (EDR) in isolated rat aortas and nitric oxide (NO) production in endothelial cells following incubation with RBCs were determined using wire myograph and DAF‐FM fluorescence. Protein levels of microR‐210 target PTP1B and the oxidative stress marker 4‐HNE were measured by immunohistochemistry. T1D RBC produced EDR and endothelial NO comparable to healthy controls, whereas T2D RBC impaired both. microR‐210 levels were similar in T1D RBC and healthy controls, but reduced in T2D RBC. microR‐210 inhibition in T1D RBC impaired EDR and increased vascular PTP1B and 4‐HNE, while PTP1B inhibition or mitoTEMPO treatment in aortas improved EDR. RBC microR‐210 regulates endothelial function differently between T1D and T2D by affecting vascular PTP1B and mitochondrial oxidative stress, highlighting a potential therapeutic target to improve vascular health.