# The Physiological Roles and Pathological Implications of Urea Transporters in the Cardiovascular System

## TL;DR

This paper reviews how urea transporters in the cardiovascular system affect heart health and disease, suggesting they could be new targets for treatment.

## Contribution

It highlights the emerging role of urea transporters in cardiovascular physiology and their potential as therapeutic targets.

## Key findings

- Urea transporters are found in heart and vascular cells, influencing cell volume and nitric oxide production.
- Disrupted urea transporter activity is linked to hypertension, heart failure, and atherosclerosis.
- Targeting urea transporters may offer new treatment strategies for cardiovascular diseases.

## Abstract

Urea transporter (UT) proteins are a group of membrane proteins specifically facilitating the transmembrane transport of urea, primarily divided into the UT-A and UT-B subfamilies. Early studies have predominantly focused on their pivotal roles in the mechanism of urine concentration in kidneys. Recently accumulating evidences suggest that UTs are also expressed in the cardiovascular system, particularly in cardiomyocytes and vascular endothelial cells, where they contribute to critical physiological processes such as regulation of cell volume homeostasis, modulation of nitric oxide production, control of myocardial electrophysiological properties, and adaptation to cardiac stress. Importantly, impairments or disruptions in UT activities have been increasingly associated with the pathogenesis and progression of multiple cardiovascular disorders, including hypertension, uremic cardiomyopathy, myocardial hypertrophy, heart failure, cardiac conduction disorders and atherosclerosis, which deepens the understanding of the role of urea metabolism as a key component in cardiovascular homeostasis. This brief review summarizes the distribution and physiological functions of UTs in the cardiovascular system, and evaluates the potential and existing challenges of targeting UTs as a novel therapeutic approach for cardiovascular diseases.