The role of uromodulin in cardiovascular disease: a review

Abstract

Uromodulin, also referred to as Tamm Horsfall protein (THP), is a renal protein exclusively synthesized by the kidneys and represents the predominant urinary protein under normal physiological conditions. It assumes a pivotal role within the renal system, contributing not only to ion transport and immune modulation but also serving as a critical factor in the prevention of urinary tract infections and kidney stone formation. Emerging evidence indicates that uromodulin may serve as a potential biomarker extending beyond renal function. Recent clinical investigations and Mendelian randomization studies have unveiled a discernible association between urinary regulatory protein levels and cardiovascular events and mortality. This review primarily delineates the intricate relationship between uromodulin and cardiovascular disease, elucidates its predictive utility as a novel biomarker for cardiovascular events, and delves into its involvement in various physiological and pathophysiological facets of the cardiovascular system, incorporating recent advancements in corresponding genetics.

Keywords: biomarker; coronary heart disease; hypertension; kidney; uromodulin.

Figure 1

Brief structure of uromodulin.

Figure 2

Mechanisms by which uromodulin affects salt-sensitive hypertension. TAL, thick ascending limb; DCT, distal convoluted tubule; TNF-α, tumor necrosis factor-α; SPAK, SPS1-associated proline/alanine-rich kinase; OSR1, oxidative stress-responsive kinase 1; NKCC2, Na + K + -2CI-cotransporter protein; NCC, Na + -CI-cotransporter protein; ENaC, epithelial sodium channel; ROMK, renal outer medullary potassium channel.

Figure 3

Mechanisms of coronary heart disease risk reduction by uromodulin. TAL, thick ascending limb; DCT, distal convoluted tubule; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides; IL-1b, interleukins-1b; TNF-α, tumor necrosis factor-α; CHD, coronary heart disease.