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Endothelial function from bench to bedside


Since 1980, the role of endothelium in the regulation vasomotor function of smooth muscle cannot be ignored. Since that time however, in addition to its vasomotor role, many other functions of endothelium have been recognized.

The first speaker of this symposium, Prof Lüscher (Zurich, CH), described the established and novel aspects of endothelial function and research achievements both in the basic and clinical fields. He gave an excellent overview of the physiological and pathophysiological mechanisms by which endothelial cells modulate vascular and tissues function. Among others, he described the role of nitric oxide, reactive oxygen species, their balance, dilator and constrictor prostaglandins, and so on. More importantly, he explained the important interactions among these systems and emphasized that endothelial cells are crucial regulators of cardiovascular homeostasis and important target of various risk factors. One of the very novel aspects of his talk was to draw a comparison between endothelial dysfunction and aging.  Accordingly, recent studies show that the aging processes of these cells are mediated - in part - by the mitochondrial adaptor protein p66, which also contributes to endothelial dysfunction in dyslipidaemia, hypertension and diabetes mellitus. Thus this mechanism and aging genes, such as p66, may represent novel targets for pharmacological intervention in the future.

The second speaker of this symposium, Prof Kupatt (Munich, DE) highlighted the importance of the interaction of endothelium and the cellular element of blood. In general, the healthy endothelium (resting condition) prevents stationary adhesion of leukocytes, monocytes and endothelial progenitor cells. However, when the endothelium and these cells became activated in various diseases the adhesion process is started, leading to extravasion and proinflammatory conditions. Although leucocytes and monocytes (macrophages) are important in the inflammation and healing process, their uncontrolled activity could lead to vascular diseases, such as atherosclerosis. One of the promising and potential future targets in this field is to control the “bad guys” (leukocytes and monocytes) and prime the “good guys”, such as endothelial progenitor cells, for example with SDF-1 or other chemokines.

Endothelial dysfunction of coronary and peripheral vessels

Next, Prof Schaechinger (Fulda, DE) described the characteristics, importance and consequences of endothelial dysfunction of coronary and peripheral vessels. Adding to the topics of the previous speakers, he emphasized the importance of assessing the function of the endothelium in clinical settings. He described the methods currently used, such as flow mediated dilation, reactive hyperaemia obtained in fingers, and intracoronary administration of vasoactive substances. He also emphasized the difficulties associated with the measurement and the interpretation of results and whether or not one can compare the results obtained in peripheral vessels to that of coronaries. He said that one has to be careful, because each vascular bed has its own specificity. What was clear from his talk is that we need to develop new methods to gain reliable data and information regarding the function/dysfunction of endothelium in humans and also look for novel factors, markers, whose levels could be related to the function of endothelium.

Finally, Prof Bugiardini (Bologna, IT) highlighted the future perspectives of the endothelial research, both in basic and clinical arenas. He also emphasized the existing gap between the findings of basic research and clinical investigations, which may prevent the development of novel therapeutic tools. This gap should be reduced by continuous discussion on both sides and by organizing symposia like this. In addition, he stated that this symposium highlighted the pivotal importance of continuous research on endothelial function and dysfunction, if we want to restore or prevent the healthy function of endothelium.

In conclusion, this session provided evidence that the endothelium should be the first line of defence in fighting cardiovascular diseases and premature aging and target for the development of new therapeutic modalities to reverse endothelial dysfunction. Although the importance of pharmacological interventions and dietary changes are well recognized, the speakers of this symposium emphasized that one of the most important stimuli to maintain healthy function of the endothelium is increasing blood flow, thereby shear stress at the luminal surface of the endothelium, thus daily exercise is one of the easiest way to improve endothelial function.

The discussion by the audience in this session was very stimulating for planning future studies on endothelial function.




Endothelial function from bench to bedside

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.