Integrated Control of Endothelial Vasoreactivity

Abstract

Extensive research over the last decades has placed the endothelium at the center of cardiovascular disease. Our and other studies clearly show an intricate control system of vasoreactivity that is the result of millions of years of evolution. This delicate system balances autocrine, paracrine and endocrine derivatives, some in the picomolar range, to maintain cardiovascular homeostasis. A trait of oxidative phosphorylation is the production of ROS and evolution has created a pallet of antioxidants throughout time to withstand oxidative and nitrosative damage. During times of endothelial damage or dysfunction, alternative pathways are activated to compensate for the altered vasoreactivity. Only when deleterious adaptations of the endothelium overcome regulatory mechanisms will the imbalance between substances with vasodilating and anti-prothrombogenic features (such as NO, and possibly H2O2), and substances with vasoconstricting (such as O2\xe2\x80\xa2\xe2\x88\x92 and ET-1) and pro-thrombotic features (such as ET-1) progress. This state, called endothelial dysfunction, will eventually lead to a myriad of cardiovascular diseases. Knowledge of its hallmark position in cardiovascular disease and assessment of its functionality, and thus placing endothelial dysfunction at the source of cardiovascular disease, already showed promising results in preventing cardiovascular disease. New knowledge now shifts the paradigm of oxidative stress from a presumed beneficial believe of total ROS eradication towards a concept of ROS adaptation and modification in cardiovascular (patho)physiology. Further, new tools are now being examined to assess endothelial function in the clinical setting and possibly use this new parameter to further prevent cardiovascular disease before it becomes overt. Detection of endothelial dysfunction, more specific the severity of endothelial dysfunction, could be a useful tool to implement in risk stratifications and possibly change treatment strategies in international guidelines