Phosphoinositide 3-kinases and their role in inflammation: potential clinical targets in atherosclerosis?

• Published in: Clinical science (1979) Vol. 116; no. 11-12; pp. 791 - 804
• Main Authors: FOUGERAT, Anne, GAYRAL, Stéphanie, MALET, Nicole, BRIAND-MESANGE, Fabienne, BRETON-DOUILLON, Monique, LAFFARGUE, Muriel
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.06.2009
• Subjects: Atherosclerosis (general aspects, experimental research); Atherosclerosis - enzymology; Atherosclerosis - immunology; Biological and medical sciences; Blood and lymphatic vessels; Blood Platelets - enzymology; Blood Platelets - immunology; Cardiology. Vascular system; Cytokines - secretion; General aspects; Humans; Inflammation; Leukocytes - enzymology; Leukocytes - immunology; Life Sciences; Macrophages - enzymology; Macrophages - immunology; Medical sciences; Neutrophils - enzymology; Neutrophils - immunology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - chemistry; Phosphatidylinositol 3-Kinases - physiology; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; atherogenesis; Targeting; Enzyme; Transferases; Rupture; plaque rupture; Cardiovascular disease; immune cells; Inflammation; Thrombosis; 1-Phosphatidylinositol 3-kinase; Vascular disease; Medicine; Target; Atherosclerosis; Cell; phosphoinositide 3-kinase
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20080549

Inflammation has a central role in the pathogenesis of atherosclerosis at various stages of the disease. Therefore it appears of great interest to develop novel and innovative drugs targeting inflammatory proteins for the treatment of atherosclerosis. The PI3K (phosphoinositide 3-kinase) family, which catalyses the phosphorylation of the 3-OH position of phosphoinositides and generates phospholipids, controls a wide variety of intracellular signalling pathways. Recent studies provide evidence for a crucial role of this family not only in immune function, such as inflammatory cell recruitment, and expression and activation of inflammatory mediators, but also in antigen-dependent responses making it an interesting target to modulate inflammatory processes. The present review will focus on the regulation of inflammation within the vasculature during atherogenesis. We will concentrate on the different functions played by each isoform of PI3K in immune cells which could be involved in this pathology, raising the possibility that inhibition of one or more PI3K isoforms may represent an effective approach in the treatment of atherosclerosis.