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. 2023 Mar 1;32(2):134-140.
doi: 10.1097/MNH.0000000000000866. Epub 2022 Dec 23.

Sortilin and hypertension

Roberta Avvisato  1   2 , Stanislovas S Jankauskas  1   2 , Fahimeh Varzideh  1   2 , Urna Kansakar  1   2 , Pasquale Mone  1   2 , Gaetano Santulli  1   2
Affiliations

Sortilin and hypertension

Roberta Avvisato et al. Curr Opin Nephrol Hypertens. .

Abstract

Purpose of review: The current review aims to present the latest scientific updates on the role of Sortilin in the pathophysiology of hypertension.

Recent findings: The main focus of this systematic overview is on the functional contribution of Sortilin to the pathogenesis of hypertension. Sortilin is a glycoprotein mostly known for its actions as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Emerging evidence indicates that Sortilin is associated with pathological conditions, including inflammation, arteriosclerosis, dyslipidemia, insulin resistance, and vascular calcification. Most recently, Sortilin has been shown to finely control endothelial function and to drive hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress.

Summary: The latest findings linking Sortilin and hypertension that are herein discussed can inspire novel areas of research which could eventually lead to the discovery of new therapeutic strategies in cardiovascular medicine.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Main signaling pathways mediated by Sortilin in the endothelial cell. aCDase, acid ceramidase; aSMase, acid sphingomyelinase; DAG, diacylglycerol; DCS, dihydroceramide synthase; DES, dihydroceramide desaturase; ER, endoplasmic reticulum; Gq, subunit q of G protein alpha; KDHR, 3-ketodihydrosphingosine reductase; NOX2, NADPH oxidase 2; PI3K, phosphatidylinositol 4,5-bisphosphate 3-kinase; PKCε, protein kinase C epsilon; PLC, phospholipase C; PYK2, protein tyrosine kinase 2 beta; ROS, reactive oxygen species; S1P, sphingosine 1 phosphate; S1PR3, type 3 sphingosine 1 phosphate receptor; SMase, sphingomyelinase; SPHK, sphingosine kinase; SPNS2, sphingolipid transporter 2; SPPase, S1P phosphatase; SPT, serine palmitoyltransferase.
FIGURE 2.
FIGURE 2.
Preclinical and clinical investigations showing that Sortilin drives arterial hypertension. (a) Sortilin induces hypertension through a mechanism that involves sphingosine-1-phosphate (S1P) lysosphingolipid receptor 3 and/or gp91phox/NOX2. (b) Circulating Sortilin levels are greater in hypertensive patients with noncontrolled hypertension and correlate with S1P levels.
FIGURE 3.
FIGURE 3.
Impact of Sortilin on cardiovascular risk. Sortilin influences cardiovascular risk acting on several organs and through different pathways.
See this image and copyright information in PMC

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