A nanomedical approach to understanding the mechanism of endothelial function and dysfunction- Clinical implications

A dysfunctional endothelium is the first step toward many diseases of modern civilization, including hypertension, coronary atherosclerosis, diabetes, obesity, heart failure, as well as aging. The development of new nanomedical devices and nanosensors allows in situ monitoring and measuring of the molecular processes in a single endothelial cell. It appears that the first step in triggering the dysfunction of endothelial cell is diminishing the release of cytoprotective molecule nitric oxide (NO). This process is coupled with the enhanced production of the cytotoxic molecules, superoxide (O2 - ) and peroxynitrite (ONOO- ). There are two major sources of the O2 - in endothelial cells: NADPH oxidase and uncoupled endothelial nitric oxide synthase (eNOS). NO is an efficient scavenger of O2 - which produces ONOO- . Peroxynitrite is a powerful oxidant and is the main component of nitroxidative stress. It appears that the damaging effects to the biological milieu are not dependent on the absolute level of ONOO- by endothelium, but rather on the ratio of NO concentration, [NO], to the concentration of ONOO- , [ONOO- ]. [NO]/ [ONOO- ] ratio can be a precise indicator of a level of endothelial dysfunction. Endothelial function and eNOS coupling can be partially restored by several currently available drugs like statins, ACE inhibitors, and β-blockers and also vitamin D3 . The restoration of functional endothelium can significantly improve a function of the cardiovascular system and inhibit progression of vascular damage due to diabetes, atherosclerosis, and aging.