Endothelial dysfunction, or the loss of proper endothelial function, is a hallmark for vascular diseases, and is often regarded as a key early event in the development of
atherosclerosis. Impaired endothelial function, causing hypertension and thrombosis, is often seen in patients with
coronary artery disease,
diabetes mellitus,
hypertension,
hypercholesterolemia, as well as in
smokers. Endothelial dysfunction has also been shown to be predictive of future adverse cardiovascular events including stroke, heart disease, and is also present in inflammatory disease such as rheumatoid arthritis, diabetes, and systemic lupus erythematosus. Endothelial dysfunction is a result of changes in endothelial function. After fat (
lipid) accumulation and when stimulated by inflammation, endothelial cells become activated, which is characterized by the expression of molecules such as E-selectin, VCAM-1 and ICAM-1, which stimulate the adhesion of immune cells. Additionally,
transcription factors, which are substances which act to increase the production of proteins within cells, become activated; specifically AP-1 and
NF-κB, leading to increased expression of cytokines such as
IL-1,
TNFα and
IFNγ, which promotes inflammation. This state of endothelial cells promotes accumulation of lipids and lipoproteins in the intima, leading to atherosclerosis, and the subsequent recruitment of white blood cells and platelets, as well as proliferation of smooth muscle cells, leading to the formation of a fatty streak. The lesions formed in the intima, and persistent inflammation lead to desquamation of endothelium, which disrupts the endothelial barrier, leading to injury and consequent dysfunction. In contrast, inflammatory stimuli also activate NF-κB-induced expression of the deubiquitinase A20 (
TNFAIP3), which has been shown to intrinsically repair the endothelial barrier. One of the main mechanisms of endothelial dysfunction is the diminishing of
nitric oxide, often due to high levels of
asymmetric dimethylarginine, which interfere with the normal
L-arginine-stimulated
nitric oxide synthesis and so leads to hypertension. The most prevailing mechanism of endothelial dysfunction is an increase in
reactive oxygen species, which can impair nitric oxide production and activity via several mechanisms. The signalling protein
ERK5 is essential for maintaining normal endothelial cell function. A further consequence of damage to the endothelium is the release of pathological quantities of
von Willebrand factor, which promote platelet aggregation and adhesion to the subendothelium, and thus the formation of potentially fatal thrombi.
Angiosarcoma is cancer of the endothelium and is rare with only 300 cases per year in the US. However it generally has poor prognosis with a five-year survival rate of 35%.
Research Cancer It has been recognised that endothelial cells building tumour vasculature have distinct morphological characteristics, different origin compared to physiological endothelium, and distinct molecular signature, which gives an opportunity for implementation of new biomarkers of tumour angiogenesis and could provide new anti-angiogenic druggable targets.
Diet A
healthy diet abundant in fruits and vegetables has a beneficial impact on endothelial function, whilst a diet high in
red and
processed meats, fried foods,
refined grains and
processed sugar increases adhesion endothelial cells and atherogenic promoters. High-fat diets adversely affect the endothelial function. A
Mediterranean diet has been found to improve endothelial function in adults which can reduce risk of cardiovascular disease.
Walnut consumption improves endothelial function.
Covid-19 In April 2020, the presence of viral elements in endothelial cells of 3 patients who had died of
COVID-19 was reported for the first time. The researchers from the
University of Zurich and
Harvard Medical School considered these findings to be a sign of a general
endotheliitis in different organs, an inflammatory response of the endothelium to the infection that can lead or at least contribute to multi-organ failure in Covid-19 patients with comorbidities such as diabetes mellitus, hypertension and cardiovascular disease. ==History==