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Interplay between the renin-angiotensin system, the canonical WNT/β-catenin pathway and PPARγ in hypertension

  • Implementation to Increase Blood Pressure Control: What Works? (J Brettler and K Reynolds, Section Editors)
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Abstract

Purpose of Review

Heterogeneous causes can determinate hypertension.

Recent Findings

The renin-angiotensin system (RAS) has a major role in the pathophysiology of blood pressure. Angiotensin II and aldosterone are overexpressed during hypertension and lead to hypertension development and its cardiovascular complications. In several tissues, the overactivation of the canonical WNT/β-catenin pathway leads to inactivation of peroxisome proliferator-activated receptor gamma (PPARγ), while PPARγ stimulation induces a decrease of the canonical WNT/β-catenin pathway. In hypertension, the WNT/β-catenin pathway is upregulated, whereas PPARγ is decreased. The WNT/β-catenin pathway and RAS regulate positively each other during hypertension, whereas PPARγ agonists can decrease the expression of both the WNT/β-catenin pathway and RAS.

Summary

We focus this review on the hypothesis of an opposite interplay between PPARγ and both the canonical WNT/β-catenin pathway and RAS in regulating the molecular mechanism underlying hypertension. The interactions between PPARγ and the canonical WNT/β-catenin pathway through the regulation of the renin-angiotensin system in hypertension may be an interesting way to better understand the actions and the effects of PPARγ agonists as antihypertensive drugs.

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Abbreviations

ACE:

angiotensin converting enzyme

APC:

adenomatous polyposis

Ang:

angiotensin

AGT:

angiotensinogen: AP-1: nuclear transcription factor activator protein 1

AT1R:

angiotensin 1 receptor

COX2:

cyclooxygenase 2

DSH:

Disheveled

FZD:

Frizzled

GSK-3β:

glycogen synthase kinase 3

LRP 5/6:

LDL receptor-related proteins 5 and 6

MI:

myocardial ischemia

NF-ϰB:

nuclear transcription factor kappaB

NOX:

NADPH oxidase

PPARγ:

peroxisome proliferator-activated receptor gamma

PRR:

pro-renin receptor

TNF:

tumor necrosis factor

RAS:

renin-angiotensin system

ROS:

reactive oxygen species

WNT:

Wingless Int.`

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  1. Paris-Descartes University; Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, Hôtel-Dieu Hospital; AP-HP, Paris, France

    Alexandre Vallée & Jacques Blacher

  2. Vessels and Blood Institute, Lariboisière University Hospital, Paris, France

    Bernard L. Lévy

  3. INSERM U970, Paris Cardiovascular Research Centre (PARCC), Paris, France

    Bernard L. Lévy

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Vallée, A., Lévy, B.L. & Blacher, J. Interplay between the renin-angiotensin system, the canonical WNT/β-catenin pathway and PPARγ in hypertension. Curr Hypertens Rep 20, 62 (2018). https://doi.org/10.1007/s11906-018-0860-4

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