Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress
Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approache...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-02-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI156624 |
| _version_ | 1828197516400656384 |
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| author | Fahimeh Varzideh Stanislovas S. Jankauskas Urna Kansakar Pasquale Mone Jessica Gambardella Gaetano Santulli |
| author_facet | Fahimeh Varzideh Stanislovas S. Jankauskas Urna Kansakar Pasquale Mone Jessica Gambardella Gaetano Santulli |
| author_sort | Fahimeh Varzideh |
| collection | DOAJ |
| description | Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. explored the signaling pathway evoked by sortilin in endothelial cells and report on such exploration in this issue of the JCI. The researchers identified circulating sortilin as a biomarker associated with high blood pressure. Mechanistically, they demonstrate that sortilin altered sphingolipid/ceramide homeostasis, initiating a signaling cascade that, from sphingosine-1-phosphate (S1P), leads to the augmented production of reactive oxygen species. Herein, we discuss the main implications of these findings, and we anticipate some of the potential avenues of investigation prompted by this discovery, which could eventually lead to treatments for cardiometabolic disorders. |
| first_indexed | 2024-04-12T10:22:02Z |
| format | Article |
| id | doaj.art-e27f62e6197c40aa85d141515ccd4c84 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-04-12T10:22:02Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-e27f62e6197c40aa85d141515ccd4c842022-12-22T03:37:05ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-02-011323Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stressFahimeh VarzidehStanislovas S. JankauskasUrna KansakarPasquale MoneJessica GambardellaGaetano SantulliSortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. explored the signaling pathway evoked by sortilin in endothelial cells and report on such exploration in this issue of the JCI. The researchers identified circulating sortilin as a biomarker associated with high blood pressure. Mechanistically, they demonstrate that sortilin altered sphingolipid/ceramide homeostasis, initiating a signaling cascade that, from sphingosine-1-phosphate (S1P), leads to the augmented production of reactive oxygen species. Herein, we discuss the main implications of these findings, and we anticipate some of the potential avenues of investigation prompted by this discovery, which could eventually lead to treatments for cardiometabolic disorders.https://doi.org/10.1172/JCI156624 |
| spellingShingle | Fahimeh Varzideh Stanislovas S. Jankauskas Urna Kansakar Pasquale Mone Jessica Gambardella Gaetano Santulli Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress The Journal of Clinical Investigation |
| title | Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress |
| title_full | Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress |
| title_fullStr | Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress |
| title_full_unstemmed | Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress |
| title_short | Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress |
| title_sort | sortilin drives hypertension by modulating sphingolipid ceramide homeostasis and by triggering oxidative stress |
| url | https://doi.org/10.1172/JCI156624 |
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