The Multifaceted Roles of PI3Kγ in Hypertension, Vascular Biology, and Inflammation

Int J Mol Sci. 2016 Nov 8;17(11):1858. doi: 10.3390/ijms17111858.

Abstract

PI3Kγ is a multifaceted protein, crucially involved in cardiovascular and immune systems. Several studies described the biological and physiological functions of this enzyme in the regulation of cardiovascular system, while others stressed its role in the modulation of immunity. Although PI3Kγ has been historically investigated for its role in leukocytes, the last decade of research also dedicated efforts to explore its functions in the cardiovascular system. In this review, we report an overview recapitulating how PI3Kγ signaling participates in the regulation of vascular functions involved in blood pressure regulation. Moreover, we also summarize the main functions of PI3Kγ in immune responses that could be potentially important in the interaction with the cardiovascular system. Considering that vascular and immune mechanisms are increasingly emerging as intertwining players in hypertension, PI3Kγ could be an intriguing pathway acting on both sides. The availability of specific inhibitors introduces a perspective of further translational research and clinical approaches that could be exploited in hypertension.

Keywords: PI3Kγ signaling; high blood pressure; immune cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / therapeutic use
  • Atherosclerosis / drug therapy
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Blood Vessels / drug effects
  • Blood Vessels / immunology
  • Blood Vessels / pathology
  • Class Ib Phosphatidylinositol 3-Kinase / genetics
  • Class Ib Phosphatidylinositol 3-Kinase / immunology*
  • Diabetic Cardiomyopathies / drug therapy
  • Diabetic Cardiomyopathies / genetics
  • Diabetic Cardiomyopathies / immunology*
  • Diabetic Cardiomyopathies / pathology
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation
  • Heart Failure / genetics
  • Heart Failure / immunology*
  • Heart Failure / pathology
  • Heart Failure / prevention & control
  • Humans
  • Hypertension / drug therapy
  • Hypertension / genetics
  • Hypertension / immunology*
  • Hypertension / pathology
  • Immunity, Innate
  • Inflammation
  • Mice
  • Phosphatidylinositol Phosphates / immunology
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Signal Transduction

Substances

  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Phosphatidylinositol Phosphates
  • Phosphoinositide-3 Kinase Inhibitors
  • Class Ib Phosphatidylinositol 3-Kinase