title: 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 blood pressure-lowering effects.
authors.affiliation: Department of Angiocardioneurology, IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Carnevale
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lembo
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects* / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D020746:Calcium Channels, L-Type; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase