Regulation of Epithelial Sodium Channel Trafficking by Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

Abstract

Background:The epithelial Na ϩ channel ENaC functions as a pathway for Na ϩ absorption across epithelia.

Pcsk9

“…(2) In the second example, within the ER/ER-Golgi intermediate compartment of cells, PCSK9 was reported to enhance the degradation of the epithelial Na + channel (ENaC) that is critical for Na + homeostasis and blood pressure control. 74 This observation was intriguing, especially in view of the expression of PCSK9 in the kidney. 12 However, our data revealed that in PCSK9-knockout mice, the basal and angiotensin-II-induced blood pressure rise is not different from wild-type controls, suggesting that EnaC levels are not appreciably increased in the absence of PCSK9, at least in mice (N.G.…”

“…12 It is also possible that PCSK9 acts locally in some extrahepatic tissues that express this protein (eg, small intestine, pancreas, and kidney), and that its circulating levels would not affect the LDLR in these tissues. The reported possible PCSK9-induced degradation of epithelial Na + channel in kidney cells 74 needs in vivo confirmation because basal blood pressure and angiotensin-II induced rise in blood pressure in mice are not modified by the lack of expression of PCSK9 (N.G. Seidah and T. Reudelhuber, unpublished data, 2014).…”

PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models of hypertension

“…It has been suggested recently that PCSK9 decreases the expression of the amiloride sensitive epithelial Na þ channel (ENaC) at the protein level [7]. As previously described for the regulation of LDLR, the catalytic activity of PCSK9 is not required for reducing ENaC cell surface expression.…”

PCSK9: A key factor modulating atherosclerosis

“…Recent studies show that PCSK9 induces degradation of epithelial Na( ) channels, which regulate blood pressure by modulating epithelial sodium reabsorption in the collecting ducts 48) . It is unclear whether this cellular observation is related to the regulation of blood pressure, but a large cohort study reported a correlation between blood pr essure and PCSK9 level 43) .…”