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Endothelial function and dysfunction
The endothelium, although only a monolayer of cells, plays a pivotal role in vascular haemostasis by regulating vascular tone, thereby controlling blood flow to end organs.1 It also plays important roles in maintaining balance between anti- and pro-coagulant activities, contributing to thrombo-resistance and controlling cellular adhesion, underlying smooth muscle proliferation, and vessel wall inflammation. In addition to local conversion of angiotensin I to angiotensin II, endothelial cells produce and release a number of vasoactive substances, including nitric oxide, endothelium derived hyperpolarising factor, prostacyclin, endothelin, and vasoconstrictor prostanoids, that regulate vascular tone. Endothelial cells can also respond to circulating vasoactive substances such as bradykinins, serotonin, adenosine, and thrombin.
Alterations in endothelial function precede the development of atherosclerotic changes in larger blood vessels, which are the common underlying pathogenetic mechanisms of a large number of diseases affecting all major organs. Endothelial dysfunction should actually be considered as endothelial activation, where there is a switch from nitric oxide mediated vasodilatation and silencing of cellular processes to activation by redox signalling. Prolonged and repeated exposure to vascular risk factors may eventually overwhelm the anti-inflammatory, vasodilatory and antiproliferative effects of normal endothelium and lead to endothelial activation and dysfunction, ultimately leading to loss of endothelial cell integrity, apoptosis and their release into the circulation. Changes in the microvasculature, through its pivotal roles in initiating and perpetuating atherosclerotic diseases in the larger conduit vessels, play an important part in the end organ damage from vascular diseases.
Understanding the importance of the endothelium in health and disease not only affords the opportunity for early detection of diseases in at-risk patients, but also provides a means for risk stratification, development of interventions to prevent disease progression and to alleviate diseases subsequent in the pathophysiological process, and the development of novel techniques to assess response to treatment.
Coronary microvascular dysfunction: clinical scenarios
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