NANOMEDICAL STUDIES OF ENDOTHELIAL AGING IN THE CARDIOVASCULAR SYSTEM (Invited Lecture)
Tadeusz Malinski, Ph.D., Ohio University, Athens, OH, USA
Background: Dysfunction of endothelium, followed by a decrease in the efficiency of the cardiovascular system, can be directly related to biological aging. The deficiency of bioavailable nitric oxide (NO) and the excessive production of peroxynitrite (ONOO-) are the most common denominators of dysfunctional endothelium. These studies elucidate the progress of endothelial dysfunction with age, as well as an increase in risk factors for cardiovascular diseases. Methods and Results: Systems of nanomedical sensors (diameter 100-300 nm) were used for the simultaneous measurements of NO, ONOO- and super oxide (O2-) concentrations and the length of telomeres in a single endothelial cell. Cellular models of human umbilical vein endothelial cells (HUVECs), as well as animal models: normotensive (WKY) and hypertensive (SHR) rats were used in these studies. We introduced the parameter of R (concentration ratio of [NO]/[O2-] + [ONOO-]) to measure the degree of endothelial dysfunction, with age, as well as the rate (K) of NO, O2- and ONOO- production (nmol/s). R value was 3.9±0.5 in young endothelium and decreased to 0.4±0.3 in aged endothelium. The rate, K, of NO release decreased during the life-span, from 200±30 nmol/s to 70±30 nmol/s. The decrease in R and K values directly correlate with the length of telomeres. Environmental factors like hypertension and diabetes further decreased both R and K values by decreasing NO availability and increasing oxidative/nitroxidative stress (O2- and ONOO-). Conclusion: The dysfunction of endothelium gradually increases with aging and is manifested by a significant decrease of bioavailable, cytoprotective NO. This effect is coupled with an increase in cytotoxic O2- and ONOO- and a decrease in the length of telomeres.