Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis.
Endothelial cells are both the source and target of factors contributing to atherosclerosis. After the discovery of the endothelium-derived relaxing factor (EDRF) by Robert F. Furchgott in 1980 it soon became clear that endothelial cells also release vasoactive factors distinct from nitric oxide (NO) namely, endothelium-derived contracting factors (EDCF) as well as hyperpolarizing factors (EDHF). Vasoactive factors derived from endothelial cells include NO/EDRF, reactive oxygen species, endothelins and angiotensins which have either EDRF or EDCF functions, cyclooxygenase-derived EDCFs and EDRFs, and EDHFs. Endothelial factors are formed by enzymes such as NO synthase, cyclooxygenase, converting enyzmes, NADPH oxidases, and epoxigenases, among others, and participate in the regulation of vascular homeostasis under physiological conditions; however, their abnormal regulation due to endothelial cell dysfunction contributes to disease processes such as atherosclerosis, arterial hypertension, and renal disease. Because of recent changes in world demographics and the declining health status of the world's population, both aging and obesity as independent risk factors for atherosclerosis-related diseases such as coronary artery disease and stroke, will continue to increase in the years to come. Obesity and associated conditions such as arterial hypertension and diabetes are now also some of the primary health concerns among children and adolescents. The similarities of pathomechanisms activated in obesity and aging suggest that obesity--at least in the vasculature--can be considered to have effects consistent with accelerated, "premature" aging. Pathomechanisms as well as the clinical issues of obesity- and aging-associated vascular changes important for atherosclerosis development and prevention are discussed.
Barton
Matthias
M
Molecular Internal Medicine, University of Zurich, LTK Y44 G22, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland. barton@access.uzh.ch
D000293:Adolescent; D000375:Aging / Q000502:physiology*; D000809:Angiotensins / Q000502:physiology; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D002648:Child; D016232:Endothelins / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D014652:Vascular Diseases / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism
D000809:Angiotensins; D016232:Endothelins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide