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

  • Alexandre Vallée
  • Bernard L. Lévy
  • Jacques Blacher
Implementation to Increase Blood Pressure Control: What Works? (J Brettler and K Reynolds, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Implementation to Increase Blood Pressure Control: What Works?


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.


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.


Hypertension Renin-angiotensin system Canonical WNT/β-catenin pathway PPARγ 



angiotensin converting enzyme


adenomatous polyposis




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


angiotensin 1 receptor


cyclooxygenase 2






glycogen synthase kinase 3

LRP 5/6

LDL receptor-related proteins 5 and 6


myocardial ischemia


nuclear transcription factor kappaB


NADPH oxidase


peroxisome proliferator-activated receptor gamma


pro-renin receptor


tumor necrosis factor


renin-angiotensin system


reactive oxygen species


Wingless Int.`


Author Contributions

All authors listed have made contribution to the work and approved it for publication.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Alexandre Vallée
    • 1
  • Bernard L. Lévy
    • 2
    • 3
  • Jacques Blacher
    • 1
  1. 1.Paris-Descartes University; Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention UnitHôtel-Dieu Hospital; AP-HPParisFrance
  2. 2.Vessels and Blood InstituteLariboisière University HospitalParisFrance
  3. 3.INSERM U970, Paris Cardiovascular Research Centre (PARCC)ParisFrance

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