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Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension

Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to regulate metabolic and cardiovascular function. Drugs...

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Autor principal: Imig, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326315/
https://www.ncbi.nlm.nih.gov/pubmed/37427406
http://dx.doi.org/10.3389/fphys.2023.1186477
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author Imig, John D.
author_facet Imig, John D.
author_sort Imig, John D.
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description Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to regulate metabolic and cardiovascular function. Drugs have been developed for nuclear receptors such as peroxisome proliferator-activated receptors (PPARα and PPARγ) and farnesoid X receptor (FXR). PPARα, PPARγ, and FXR agonists are used clinically to treat lipid disorders and metabolic diseases. Evidence from clinical studies and animal hypertension models have demonstrated that PPARα, PPARγ, and FXR agonism can lower blood pressure and decrease end organ damage which could be useful for the treatment of hypertension in patients with metabolic diseases. Unfortunately, PPAR and FXR agonists have unwanted clinical side effects. There have been recent developments to limit side effects for PPAR and FXR agonists. Combining PPAR and FXR agonism with soluble epoxide hydrolase (sEH) inhibition or Takeda G protein receptor 5 (TGR5) agonism has been demonstrated in preclinical studies to have actions that would decrease clinical side effects. In addition, these dual modulating drugs have been demonstrated in preclinical studies to have blood pressure lowering, anti-fibrotic, and anti-inflammatory actions. There is now an opportunity to thoroughly test these novel dual modulators in animal models of hypertension associated with metabolic diseases. In particular, these newly developed dual modulating PPAR and FXR drugs could be beneficial for the treatment of metabolic diseases, organ fibrosis, and hypertension.
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spelling pubmed-103263152023-07-08 Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension Imig, John D. Front Physiol Physiology Hypertension characterized by an elevated blood pressure is a cardiovascular disease that afflicts greater than one in every three adults worldwide. Nuclear receptors are large superfamily of DNA-binding transcription factors that target genes to regulate metabolic and cardiovascular function. Drugs have been developed for nuclear receptors such as peroxisome proliferator-activated receptors (PPARα and PPARγ) and farnesoid X receptor (FXR). PPARα, PPARγ, and FXR agonists are used clinically to treat lipid disorders and metabolic diseases. Evidence from clinical studies and animal hypertension models have demonstrated that PPARα, PPARγ, and FXR agonism can lower blood pressure and decrease end organ damage which could be useful for the treatment of hypertension in patients with metabolic diseases. Unfortunately, PPAR and FXR agonists have unwanted clinical side effects. There have been recent developments to limit side effects for PPAR and FXR agonists. Combining PPAR and FXR agonism with soluble epoxide hydrolase (sEH) inhibition or Takeda G protein receptor 5 (TGR5) agonism has been demonstrated in preclinical studies to have actions that would decrease clinical side effects. In addition, these dual modulating drugs have been demonstrated in preclinical studies to have blood pressure lowering, anti-fibrotic, and anti-inflammatory actions. There is now an opportunity to thoroughly test these novel dual modulators in animal models of hypertension associated with metabolic diseases. In particular, these newly developed dual modulating PPAR and FXR drugs could be beneficial for the treatment of metabolic diseases, organ fibrosis, and hypertension. Frontiers Media S.A. 2023-06-23 /pmc/articles/PMC10326315/ /pubmed/37427406 http://dx.doi.org/10.3389/fphys.2023.1186477 Text en Copyright © 2023 Imig. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Imig, John D.
Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
title Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
title_full Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
title_fullStr Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
title_full_unstemmed Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
title_short Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension
title_sort peroxisome proliferator-activated receptors, farnesoid x receptor, and dual modulating drugs in hypertension
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326315/
https://www.ncbi.nlm.nih.gov/pubmed/37427406
http://dx.doi.org/10.3389/fphys.2023.1186477
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