PI3Kγ in hypertension: A novel therapeutic target controlling vascular myogenic tone and target organ damage

Abstract

In the past decade, several studies have characterized a number of cellular and molecular mechanisms that contribute to the regulation of the vascular myogenic response, thus affecting blood pressure regulation. Recently, phosphoinositide 3-kinase γ (PI3Kγ) has been identified as a main regulator of vascular myogenic tone and blood pressure, a result further strengthened by a highly significant genome-wide association of a single nucleotide polymorphism flanking this gene with blood pressure regulation, in a large human population. The goal of this review is to summarize the available information regarding the mechanism whereby PI3Kγ exerts blood pressure control, regulating myogenic tone at the level of L-type calcium channel in smooth muscle cells. Moreover, an overview of the pharmacological approaches available for targeting this signalling pathway shows that PI3Kγ is a suitable candidate for antihypertensive therapy, capable of lowering blood pressure. Finally, a survey of the studies dissecting the role of PI3Kγ in pathological conditions that are typically induced by hypertension in its target organs provides a more complete picture of the high potential of this novel therapeutic approach for fighting hypertension and, at the same time, its target organ damage, independently of bloodpressure-lowering effects. © 2012 The Author.