Nephrol Dial Transplant (2002) 17: 2055-2064
© 2002 European Renal Association-European Dialysis and Transplant Association
Invited Comment
Atherogenesis—recent insights into basic mechanisms and their clinical impact
Department of Medicine IV, Division of Cardiology, J. W. Goethe University, Frankfurt am Main, Germany
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Initial step in atherogenesis—impairment of endothelial function
Prior to the development of atherosclerotic plaques, endothelial vasodilator function is impaired early in the process of atherogenesis. The endothelium is not only a single cell layered mechanical barrier between the blood and vessel wall, but regulates various important functions of the vasculature such as vasomotion and, therefore, blood flow regulation, as well as haemostasis and wall proliferation processes.
To control vasomotor tone, the endothelium releases a variety of substances, such as prostacyclin, hyperpolarizing factor, endothelin and, most importantly, nitric oxide (NO) [1]. Physiologically, exercise is an important mechanical endothelial stimulus mediated by shear stress due to increased blood flow: the flow-dependent dilation of pre-capillary resistance as well as conductance vessels allows blood flow to increase according to metabolic demand. Whereas increased blood flow stimulates the endothelium mechanically, other stimuli such as catecholamines, bradykinin or platelet-released serotonin stimulate specific receptors on endothelial cells. If the integrity of the
Nitric oxide
NO inactivation due to oxidative stress
Reduced NO production
NO is not equal to NO
Basic mechanisms of endothelial activation in atherosclerosis
Inflammation
Proliferation
Apoptosis
Endothelial activation and clinical manifestations of atherosclerosis
Prognostic relevance of endothelial vasodilator dysfunction
Treatment of endothelial activation
Statins
ACE-inhibitors and angiotensin blockers
Vitamins and hormones
Perspectives
Risk stratification
Guidance of therapy
New therapeutic concepts
Anti-inflammatory therapy
Gene therapy
Stem cell therapy
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