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Role of the Peroxisome Proliferator Activated Receptors in Hypertension. Circ Res 2021 04 02;128(7):1021-1039

Date

04/02/2021

Pubmed ID

33793338

Pubmed Central ID

PMC8020861

DOI

10.1161/CIRCRESAHA.120.318062

Scopus ID

2-s2.0-85103807023   4 Citations

Abstract

Nuclear receptors represent a large family of ligand-activated transcription factors which sense the physiological environment and make long-term adaptations by mediating changes in gene expression. In this review, we will first discuss the fundamental mechanisms by which nuclear receptors mediate their transcriptional responses. We will focus on the PPAR (peroxisome proliferator-activated receptor) family of adopted orphan receptors paying special attention to PPARγ, the isoform with the most compelling evidence as an important regulator of arterial blood pressure. We will review genetic data showing that rare mutations in PPARγ cause severe hypertension and clinical trial data which show that PPARγ activators have beneficial effects on blood pressure. We will detail the tissue- and cell-specific molecular mechanisms by which PPARs in the brain, kidney, vasculature, and immune system modulate blood pressure and related phenotypes, such as endothelial function. Finally, we will discuss the role of placental PPARs in preeclampsia, a life threatening form of hypertension during pregnancy. We will close with a viewpoint on future research directions and implications for developing novel therapies.

Author List

Fang S, Livergood MC, Nakagawa P, Wu J, Sigmund CD

Authors

Mary Christine Livergood MD Adjunct Instructor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Brain
Female
Humans
Hypertension
Immune System
Kidney
Mice
PPAR gamma
Peroxisome Proliferator-Activated Receptors
Placenta
Pre-Eclampsia
Pregnancy
Rats
Research
Transcription Factors