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 discusse

In Memoriam: Wolfgang Kiowski, M.D. (1949–2012) - Pioneer in clinical endothelin research

AbstractWolfgang Kiowski, M.D. (1949–2012) was a German physician-scientist who made exemplary contributions to clinical research in human physiology, heart failure, arterial hypertension, and endothelin science. His academic career took him from Heinz Losse, M.D. at the University of Münster, Germany, to the University of Michigan, U.S.A., to work with Stevo Julius, M.D. In 1979, Kiowski was recruited to the University of Basel in Switzerland and ultimately moved to the Hospital of the University of Zürich in Switzerland. Twenty years ago, Kiowski published a landmark study pioneering the use of endothelin receptor antagonists (ERAs) in patients (Lancet 1995; 346: 732–736), which introduced a new therapeutic principle to human medicine. During his career, he published numerous studies in the area of pathophysiology, clinical pharmacology (particularly calcium channel blockers, ERAs, and PDE5 inhibitors), heart failure, cardiac transplantation, coronary artery disease, and many case reports from his clinical work. Kiowski was an active mentor and trained many young physicians and physician-scientists. He died unexpectedly in Zürich during the planning stages of the Thirteenth International Conference on Endothelin to be held in Tokyo in 2013. This article summarizes Kiowski's achievements, his role as a mentor and as the human being he was. He will be remembered as a role model of an outstanding, curious clinician who was highly successful as a physician, scientist, and teacher, and at the same time managed to enjoy many hobbies and life with his family. Referring to Wolfgang Kiowski, the article closes with a “It can be done!”—message to young physician-scientists by Dr. Stevo Julius