Abstract
Chronic kidney disease (CKD) is associated with excessive cardiovascular disease and mortality. Nitric oxide (NO) – soluble guanylate cyclase (sGC) signaling is impaired in CKD patients, contributing to a near ubiquitous endothelial dysfunction. Loss of kidney function induces major alterations in the blood concentration of numerous molecules. Several of these so-called uremic retention solutes are known to interfere with NO-sGC signaling. p-Cresol/p-cresyl sulfate (PCS), a prototypic representative of the protein-bound uremic retention solutes, is independently associated with overall mortality and incident cardiovascular disease in hemodialysis patients. The mechanisms underlying this association remain elusive. We hypothesized that PCS interferes with NO-sGC signaling, thereby contributing to CKD-associated endothelial dysfunction and cardiovascular mortality.
Highlights
Chronic kidney disease (CKD) is associated with excessive cardiovascular disease and mortality
Loss of kidney function induces major alterations in the blood concentration of numerous molecules. Several of these so-called uremic retention solutes are known to interfere with Nitric oxide (NO)-soluble guanylate cyclase (sGC) signaling. p-Cresol/ p-cresyl sulfate (PCS), a prototypic representative of the protein-bound uremic retention solutes, is independently associated with overall mortality and incident cardiovascular disease in hemodialysis patients
We investigated the effects of PCS on NO and cGMP generation and on eNOS, sGC and caveolin-1 expression by human umbilical vein endothelial cells (HUVEC)
Summary
Chronic kidney disease (CKD) is associated with excessive cardiovascular disease and mortality. Nitric oxide (NO) – soluble guanylate cyclase (sGC) signaling is impaired in CKD patients, contributing to a near ubiquitous endothelial dysfunction. Loss of kidney function induces major alterations in the blood concentration of numerous molecules. Several of these so-called uremic retention solutes are known to interfere with NO-sGC signaling. P-Cresol/ p-cresyl sulfate (PCS), a prototypic representative of the protein-bound uremic retention solutes, is independently associated with overall mortality and incident cardiovascular disease in hemodialysis patients. The mechanisms underlying this association remain elusive. We hypothesized that PCS interferes with NO-sGC signaling, thereby contributing to CKD-associated endothelial dysfunction and cardiovascular mortality
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