CaM Kinase II-dependent pathophysiological signalling in endothelial cells.
Calcium/calmodulin-dependent protein kinase II (CaM Kinase II) is a known modulator of cardiac pathophysiology. The present review uniquely focuses on novel CaM Kinase II-mediated endothelial cell signalling which, under pathophysiological conditions, may indirectly modulate cardiac functions via alterations in endothelial or endocardial responses. CaM Kinase II has four different isoforms and various splicing variants for each isoform. The endothelial cell CaM Kinase II isoforms are sensitive to KN93 and a threonine 286-mutated inhibitory peptide. In macrovascular endothelial cells derived from aortas, CaM Kinase II mediates redox-sensitive upregulation of endothelial nitric oxide synthase (eNOS) gene expression by hydrogen peroxide (H2O2) and oscillatory shear stress, and a rapid activation of eNOS in response to bradykinin. In endothelial cells derived from lung microvessels, CaM Kinase II mediates barrier dysfunction, particularly when activated by thrombin. In brain capillary endothelial cells, CaM Kinase II lies upstream of voltage-gated potassium channels and hypoxia-induced cell swelling. In both macrovascular and microvascular endothelial cells, CaM Kinase II mediates actin cytoskeleton reorganization via distinct p38 MAPK/HSP27 and ERK1/2/MLCK signalling pathways, respectively. Although understanding of endothelium-specific CaM Kinase II signalling is nascent, data accumulated so far have demonstrated a potentially significant role of CaM Kinase II in endothelial cell pathophysiology.
Cai
Hua
H
Division of Molecular Medicine, Cardiovascular Research Laboratories, Department of Anesthesiology, David Geffen School of Medicine, University of California Los Angeles , 650 Charles E Young Drive, Los Angeles, CA 90095, USA. hcai@mednet.ucla.edu
Liu
Depei
D
Garcia
Joe G N
JG
D000199:Actins / Q000378:metabolism; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008833:Microcirculation / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D014664:Vasodilation
D000199:Actins; D007527:Isoenzymes; D052250:Nitric Oxide Synthase Type III; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2