# Human Left Ventricle circRNA-miRNA-mRNA Network Analyses Reveal a Novel Proangiogenic Role for circNPHP1 Under Ischemic Conditions

## TL;DR

This study identifies a new RNA network in heart disease and diabetes that could help develop treatments to improve blood vessel growth.

## Contribution

The study reveals a novel proangiogenic role for circNPHP1 in cardiac endothelial cells under ischemic and diabetic conditions.

## Key findings

- CircNPHP1 promotes angiogenesis by sponging miR-221-3p in ischemic and diabetic conditions.
- The circNPHP1-miR-221-3p-BCL2-VEGFA subnetwork is involved in endothelial cell proliferation and angiogenesis.
- CircNPHP1 is identified as a potential therapeutic target for promoting blood vessel growth in heart disease.

## Abstract

•We found a novel circRNA-miRNA-mRNA network in IHD and T2DM.•CircNPHP1 regulates angiogenesis and proliferation in the cardiac endothelial cells exposed to conditions mimicking IHD and T2DM.•We elucidated a novel proangiogenic subnetwork consisting of circNPHP1, miR-221-3p, BCL2, and VEGFA.•We identified circNPHP1 as a potential new target for therapeutic angiogenesis.

We found a novel circRNA-miRNA-mRNA network in IHD and T2DM.

CircNPHP1 regulates angiogenesis and proliferation in the cardiac endothelial cells exposed to conditions mimicking IHD and T2DM.

We elucidated a novel proangiogenic subnetwork consisting of circNPHP1, miR-221-3p, BCL2, and VEGFA.

We identified circNPHP1 as a potential new target for therapeutic angiogenesis.

Therapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and type 2 diabetes mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM, and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells. We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2, in IHD and T2DM.