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Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension
Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954306/ https://www.ncbi.nlm.nih.gov/pubmed/36831252 http://dx.doi.org/10.3390/cells12040585 |
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author | Chechekhin, Vadim Ivanova, Anastasia Kulebyakin, Konstantin Sysoeva, Veronika Naida, Daria Arbatsky, Mikhail Basalova, Nataliya Karagyaur, Maxim Skryabina, Mariya Efimenko, Anastasia Grigorieva, Olga Kalinina, Natalia Tkachuk, Vsevolod Tyurin-Kuzmin, Pyotr |
author_facet | Chechekhin, Vadim Ivanova, Anastasia Kulebyakin, Konstantin Sysoeva, Veronika Naida, Daria Arbatsky, Mikhail Basalova, Nataliya Karagyaur, Maxim Skryabina, Mariya Efimenko, Anastasia Grigorieva, Olga Kalinina, Natalia Tkachuk, Vsevolod Tyurin-Kuzmin, Pyotr |
author_sort | Chechekhin, Vadim |
collection | PubMed |
description | Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases vasoconstriction via α1-adrenoceptor activation on vascular cells. Despite the fact that a sympathetic outflow increases in individuals with obesity, as a rule, there is a cohort of patients with obesity who do not develop hypertension. In this study, we investigated how adrenoceptors’ expression and functioning in adipose tissue are affected by obesity-driven hypertension. Here, we demonstrated that α1A is a predominant isoform of α1-adrenoceptors expressed in the adipose tissue of patients with obesity, specifically by multipotent mesenchymal stromal cells (MSCs). These cells respond to prolonged exposure to noradrenaline in the model of sympathetic overdrive through the elevation of α1A-adrenoceptor expression and signaling. The extent of MSCs’ response to noradrenaline correlates with a patient’s arterial hypertension. scRNAseq analysis revealed that in the model of sympathetic overdrive, the subpopulation of MSCs with contractile phenotype expanded significantly. Elevated α1A-adrenoceptor expression is triggered specifically by beta3-adrenoceptors. These data define a novel pathophysiological mechanism of obesity-driven hypertension by which noradrenaline targets MSCs to increase microvessel constrictor responsivity. |
format | Online Article Text |
id | pubmed-9954306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99543062023-02-25 Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension Chechekhin, Vadim Ivanova, Anastasia Kulebyakin, Konstantin Sysoeva, Veronika Naida, Daria Arbatsky, Mikhail Basalova, Nataliya Karagyaur, Maxim Skryabina, Mariya Efimenko, Anastasia Grigorieva, Olga Kalinina, Natalia Tkachuk, Vsevolod Tyurin-Kuzmin, Pyotr Cells Article Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases vasoconstriction via α1-adrenoceptor activation on vascular cells. Despite the fact that a sympathetic outflow increases in individuals with obesity, as a rule, there is a cohort of patients with obesity who do not develop hypertension. In this study, we investigated how adrenoceptors’ expression and functioning in adipose tissue are affected by obesity-driven hypertension. Here, we demonstrated that α1A is a predominant isoform of α1-adrenoceptors expressed in the adipose tissue of patients with obesity, specifically by multipotent mesenchymal stromal cells (MSCs). These cells respond to prolonged exposure to noradrenaline in the model of sympathetic overdrive through the elevation of α1A-adrenoceptor expression and signaling. The extent of MSCs’ response to noradrenaline correlates with a patient’s arterial hypertension. scRNAseq analysis revealed that in the model of sympathetic overdrive, the subpopulation of MSCs with contractile phenotype expanded significantly. Elevated α1A-adrenoceptor expression is triggered specifically by beta3-adrenoceptors. These data define a novel pathophysiological mechanism of obesity-driven hypertension by which noradrenaline targets MSCs to increase microvessel constrictor responsivity. MDPI 2023-02-11 /pmc/articles/PMC9954306/ /pubmed/36831252 http://dx.doi.org/10.3390/cells12040585 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chechekhin, Vadim Ivanova, Anastasia Kulebyakin, Konstantin Sysoeva, Veronika Naida, Daria Arbatsky, Mikhail Basalova, Nataliya Karagyaur, Maxim Skryabina, Mariya Efimenko, Anastasia Grigorieva, Olga Kalinina, Natalia Tkachuk, Vsevolod Tyurin-Kuzmin, Pyotr Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension |
title | Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension |
title_full | Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension |
title_fullStr | Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension |
title_full_unstemmed | Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension |
title_short | Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension |
title_sort | alpha1a- and beta3-adrenoceptors interplay in adipose multipotent mesenchymal stromal cells: a novel mechanism of obesity-driven hypertension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9954306/ https://www.ncbi.nlm.nih.gov/pubmed/36831252 http://dx.doi.org/10.3390/cells12040585 |
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