Role of the Peroxisome Proliferator Activated Receptors in Hypertension

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 PPAR gamma, 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 PPAR gamma cause severe hypertension and clinical trial data which show that PPAR gamma 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.

Automated summary

This review focuses on the mechanisms by which nuclear receptors mediate transcriptional responses, with a specific emphasis on the role of PPARγ in regulating blood pressure. Genetic and clinical trial data demonstrate the importance of PPARγ in hypertension, and the tissue- and cell-specific molecular mechanisms by which PPARs modulate blood pressure and related phenotypes are detailed. The role of placental PPARs in preeclampsia is also discussed, along with future research directions and implications for novel therapies.