Endothelial function and pathogenesis of endothelial dysfunction

Abstract

Background: The crucial role of endothelium is due to the ability of endothelial cells to receive and concurrently respond to humoral and hemodynamic stimuli. The mechanisms that mediate these reactions are: the production of endothelium-derived factors and metabolizing enzymes; the expression of binding proteins and adhesive molecules; and the consequential shape changes. In fact, a wide range of anti-atherosclerotic action substances is produced by the endothelial cells with the objective of maintaining the balance between vasoconstriction and vasodilation, and inhibit or stimulate the proliferation and migration of smooth muscle cells, thrombogenesis and fibrinolysis. Smoke, age, hypercholesterolemia, hypertension, hyperglycemia, and a family history of atherosclerotic disease may induce functional and structural changes in the endothelium that imply the progressive loss of its protective role and the development of a proatherosclerotic state called endothelial dysfunction. Methods: The evaluation of the function of endothelial cells is based on the measurement of endothelial cell response to the stimulation by vasoactive substances. The endothelial response can be assessed in the coronary arteries and peripheral circulations. On our opinion, among the techniques, the most advantageous, reproducible, minimally invasive and statistically valid, as shown in many trials, is the Endo-PAT. This technique assesses endothelial function on peripheral arteries evaluating, at the level of the distal phalanx of the index finger, the vascular response to a period of ischemia in the arm induced through occlusion of the brachial artery (for five minutes) and subsequent restoration of blood flow. An additional method that is used to evaluate the state of wellness of large arteries is arterial stiffness. Arterial stiffness can be described as a reduced capability of a vessel to dilate or contract in response to pressure changes; it is defined using two parameters: compliance and distensibility. Result and Conclusion: The present review intends to clarify the mechanisms behind the development of endothelial dysfunction, and aims to show how widely proven is the correlation between endothelial dysfunction (assessed both by Endo-PAT and sphigmoCOR) and cardiovascular diseases, such as atherosclerosis, hypertension, diabetes mellitus, stroke, coronary artery disease and heart failure. Moreover, the assessment of endothelial dysfunction may represent an integral adjuvant test to identify the predisposed patients at risk for future cardiovascular accidents, as we suggest.