Published online before print January 6, 2005, doi: 10.1161/01.ATV.0000155325.41507.e0
© 2005 American Heart Association, Inc.
Brief Reviews |
Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance
From Joslin Diabetes Center, Harvard Medical School, Boston, Mass.
Correspondence to George L. King, MD, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Room 4504, Boston, MA 02120. E-mail george.king{at}joslin.harvard.edu
Series Editor: Richard A. Cohen
Diabetic Vascular Disease: Pathophysiological Mechanisms in the Diabetic Milieu and Therapeutic Implications
ATVB In Focus
Previous Brief Reviews in this Series:
•Naka Y, Bucciarelli LG, Wendt T, Lee LK, Rong LL, Ramasamy R, Yan SF, Schmidt AM. RAGE axis: animal models and novel insights into the vascular complications of diabetes. 2004;24:1342–1349.
•Natarajan R, Nadler JL. Lipid inflammatory mediators in diabetic vascular disease. 2004;24:1542–1548.
In diabetes and insulin resistance, activation of protein kinase C (PKC) in vascular cells may be a key link between elevated plasma and tissue concentrations of glucose and nonesterified fatty acids and abnormal vascular cell signaling. Initial studies of PKC activation in diabetes focused on microvascular complications, but increasing evidence supports that PKC plays a role in several mechanisms promoting atherosclerosis. This review explains how PKC is thought to be activated in diabetes and insulin resistance through de novo synthesis of diacylglycerol. Furthermore, the review summarizes studies that implicate PKC in promoting proatherogenic mechanisms or inhibiting antiatherogenic mechanisms, including studies of endothelial dysfunction; gene induction and activation of vascular NAD(P)H oxidase; endothelial nitric oxide synthase expression and function; endothelin-1 expression; growth, migration, and apoptosis of vascular smooth muscle cells; induction of adhesion molecules; and oxidized low-density lipoprotein uptake by monocyte-derived macrophages.
In diabetes and insulin resistance, activation of PKC in vascular cells may be a key link between elevated plasma and tissue concentrations of glucose and nonesterified fatty acids and abnormal vascular cell signaling. This review summarizes studies that implicate PKC in promoting proatherogenic mechanisms or inhibiting antiatherogenic mechanisms.
Key Words: pathophysiology • cell signaling/signal transduction • gene regulation • type 2 diabetes • mechanism of atherosclerosis/growth factors • type 1 diabetes • endothelium/vascular type/nitric oxide
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