Endothelial cells LEENE on noncoding RNAs in diabetic vasculopathy
Aneesh Kallapur, Tamer Sallam
Aneesh Kallapur, Tamer Sallam
Published February 1, 2023
Citation Information: J Clin Invest. 2023;133(3):e167047. https://doi.org/10.1172/JCI167047.
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Endothelial cells LEENE on noncoding RNAs in diabetic vasculopathy

Abstract

Long noncoding RNAs (lncRNAs) have emerged as key mediators of regulated gene expression in diverse biologic contexts, including cardiovascular disease. In this issue of the JCI, Tang, Luo, and colleagues explored the contributions of lncRNAs in diabetic vasculopathy. The authors identified the lncRNA LEENE as a key mediator of angiogenesis and ischemic response. In a model of diabetic peripheral arterial disease, loss of LEENE led to impaired vascular perfusion, while its overexpression rescued the ischemic defect. The authors used unbiased chromatin affinity assays to decipher LEENE’s interactome and mode of action. These findings offer insights as to why patients with diabetes are uniquely susceptible to developing peripheral vascular disease and fill important gaps in our understanding of mechanisms that connect metabolic dysregulation with impaired angiogenesis.

Authors

Aneesh Kallapur, Tamer Sallam

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Figure 1

LEENE induces angiogenesis in peripheral arterial disease.

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LEENE induces angiogenesis in peripheral arterial disease. Metabolic dis...
Metabolic disruption, such that which occurs in diabetes, often results in impaired angiogenesis, and patients with diabetes have increased risk for limb ischemia. LEENE is downregulated by hyperglycemia and inflammation and upregulated by hypoxia. Loss of LEENE decreases angiogenesis and increases ischemic recovery time. In contrast, increasing LEENE levels improves these defects despite diabetic conditions, providing a target for peripheral arterial disease.