Linking endothelial dysfunction with endothelial cell activation.

The thin layer of cells that lines the interior of blood vessels, known as the endothelium, plays a complex role in vascular biology. The endothelium mediates blood vessel tone, hemostasis, neutrophil recruitment, hormone trafficking, and fluid filtration. Endothelial dysfunction, as defined by a lack of NO, has been linked to a variety of disease states, including atherosclerosis, diabetes mellitus, coronary artery disease, hypertension, and hypercholesterolemia. Indeed, restoration of endothelial function is one of the earliest recognizable benefits of statin therapy. In 1995, James Liao and colleagues published a study in the JCI demonstrating that NO is a vascular protective factor that limits endothelial activation and prevents leukocyte adhesion to the vessel wall.

[1]  B. Lévy,et al.  Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  S. Moncada,et al.  Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis. , 2005, European heart journal.

[3]  François Mach,et al.  Inflammation and Atherosclerosis , 2004, Herz.

[4]  Paul L Huang,et al.  Accelerated Atherosclerosis, Aortic Aneurysm Formation, and Ischemic Heart Disease in Apolipoprotein E/Endothelial Nitric Oxide Synthase Double-Knockout Mice , 2001, Circulation.

[5]  P. Baeuerle IκB–NF-κB Structures At the Interface of Inflammation Control , 1998, Cell.

[6]  M. Gimbrone,et al.  Biomechanical activation: an emerging paradigm in endothelial adhesion biology. , 1997, The Journal of clinical investigation.

[7]  P. Libby,et al.  Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. , 1995, The Journal of clinical investigation.

[8]  J. Liao,et al.  Oxidized Low-density Lipoprotein Decreases the Expression of Endothelial Nitric Oxide Synthase (*) , 1995, The Journal of Biological Chemistry.

[9]  M. Yoshizumi,et al.  Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. , 1993, Circulation research.

[10]  D. Harrison,et al.  Hypercholesterolemia increases endothelial superoxide anion production. , 1993, The Journal of clinical investigation.

[11]  P. Libby,et al.  An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[12]  P. Kubes,et al.  Nitric oxide: an endogenous modulator of leukocyte adhesion. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Moncada,et al.  Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor , 1986, Nature.

[14]  P. Baeuerle IkappaB-NF-kappaB structures: at the interface of inflammation control. , 1998, Cell.