Edited by:Mohammad Hezarkhani MD,Urologist
Board-Certified of Urology,Tehran University ,The Member of Iranian Urological Association
Madaen Hospital Tehran Iran
Mohammad.hezarkhani@yahoo.com
www.facebook.com/mohammad.hezarkhani.1
14 April 2013
Endothelial Functions
A single layer of endothelial cells lines the entire vascular system. In adults, approximately ten trillion (1013) cells form an almost 1 kg ‘organ’. Endothelial cell structure and functional integrity are important in the maintenance of the vessel wall and circulatory function, but the endothelium is by no means inert.
As a barrier, the endothelium is semi‐permeable and regulates the transfer of small and large molecules. Endothelial cells are dynamic and have both metabolic and synthetic functions.
Endothelium transport functions:
The endothelium is an important barrier to the free passage of molecules and cells from the blood to the underlying interstitium and cells. Specific transport mechanisms transport essential circulating blood macromolecules across endothelial cells to the subendothelial space to meet the metabolic needs of the surrounding tissue cells .In addition, the junctions between endothelial cells (the ‘tight’ junctions) act as a selective barrier to the egress of molecules from the circulation.
1-Glucose transport
2-Amino acid transport
3-Caveolae(Caveolae are invaginations in the cell membrane and are important vesicle carriers responsible for transcellular transport (transcytosis) in endothelial cells).
4-Tight junctions(Tight junctions are intercellular junctions important for paracellular transport. Although vascular permeability depends on both the paracellular pathway (tight junctions) and transcellular pathway (caveolae) of the endothelium, oedema develops mainly as a result of dysfunction of tight junctions).
Vascular Tone:
The endothelium produces a number of vasodilator and vasoconstrictor substances which regulate vasomotor tone and the recruitment and activity of inflammatory cells, and regulate thrombosis.
1-Nitric oxide
2-Endothelin
3-Leukotrienes
Host Defence:
Endothelial cells are in a unique strategic position as key players in host defence and inflammation. Orchestration of immune and inflammatory responses depends on communication between cells by soluble molecules given the generic terms cytokines; these include chemokines, colony stimulating factors (CSF), IL, growth factors and interferons (IFN). They are low‐molecular‐weight proteins that regulate both the amplitude and duration of the immune and inflammatory responses. Endothelial cells produce and react to a variety of cytokines and other mediators.
Haemostasis and coagulation:
Coagulation‐related receptors on the surface of vascular cells and circulating coagulation proteins are tightly controlled, to regulate coagulation and initiate a coagulation response to vascular injury. Endothelial and smooth muscle cells express a variety of proteins directly participating in haemostasis.
Angiogenesis:
Vascular endothelial growth factor (VEGF) is an angiogenic factor produced by a variety of cells, including endothelial cells, with specific receptors on the endothelium. Angiogenesis – the formation of new blood vessels from pre‐existing endothelium – is mediated by VEGF. VEGF contributes to the inflammatory response through stimulation of the release of adhesion molecules, metalloproteinases and nitric oxide, via the transcription factor activator protein‐1 (AP‐1).
Endothelial Dysfunction
Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types.
The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation.
Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone.
Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells.
Endothelial dysfunction can result from and/or contribute to several disease processes, as occurs in hypertension, hypercholesterolaemia, diabetes, septic shock, Behcet's disease, and it can also result from environmental factors, such as from smoking tobacco products and exposure to air pollution. Endothelial dysfunction is more prevalent in shift workers, a group known to have a higher risk for cardiovascular diseases. Endothelial dysfunction is a major physiopathological mechanism that leads towards coronary artery disease, and other atherosclerotic diseases.
Endothelial dysfunction is thought to be a key event in the development of atherosclerosis and predates clinically obvious vascular pathology by many years.
This is because endothelial dysfunction is associated with reduced anticoagulant properties as well as increased adhesion molecule expression, chemokine and other cytokine release, as well as reactive oxygen species production from the endothelium. This leads to inflammation and myofibroblast migration and proliferation inside the vessel all of which play important roles in the development of atherosclerosis.
In fact, endothelial dysfunction has been shown to be of prognostic significance in predicting independently vascular events including stroke and myocardial infarction. Because of this, endothelial function testing have great potential prognostic value for the early detection of cardiovascular disease; clinical trials in the recent years have demonstrated the feasibility of translating this measurement to the clinical practice.
Nitric Oxide (NO) reduction is considered the hallmark of endothelial dysfunction A key and quantifiable feature of endothelial dysfunction is the inability of arteries and arterioles to dilate fully in response to an appropriate stimulus that stimulates release of vasodilators from the endothelium like NO.
Endothelial dysfunction is commonly associated with decreased NO bioavailability, which is due to impaired NO production by the endothelium and/or increased inactivation of NO by reactive oxygen species.
This can be tested by a variety of methods including iontophoresis of acetylcholine, direct administration of various vasoactive agents to segments of blood vessels, localised heating of the skin and temporary arterial occlusion by inflating a blood pressure cuff to high pressures. Testing can also take place in the coronary arteries themselves but this is invasive and not normally conducted unless there is a clinical reason for intracoronary catheterisation.
Of all the current tests employed in the research setting, flow-mediated dilation is the most widely used non-invasive test for assessing endothelial function. This technique measures endothelial function by inducing reactive hyperemia via temporary arterial occlusion and measuring the resultant relative increase in blood vessel diameter via ultrasound.
Measurement of endothelial function by Peripheral arterial tonometry or endopat, is also mediated by a NO response. As people with endothelial dysfunction have low NO bioavailability, their blood vessels have a decreased capacity to dilate in response to certain stimuli, compared to those with normal endothelial function.
In order to properly perform a test for endothelial dysfunction, patients must avoid having certain medications and food at least 12 hours prior to the test; temperature must be controlled (at room temperature) ,and ideally should be performed at the same time in the same patient due to circadian rhythms.
NO has the following physiological effects that contribute to the inhibition of atherosclerosis:
1) NO is released and produces vasodilation after shear stress in the vessel; the vasodilation NO mediated-response in turns decreases the shear stress. If the shear stress is chronically induced it leads to the upregulation of and release of inflammatory cytokines 2) NO decreases LDL oxidation; 3) NO reduces platelet aggregation to the endothelium 4) NO Inhibits smooth muscle cell proliferative 5) NO prevents leukocyte adhesion and infiltration into the vessel.
Endothelial dysfunction, a marker for atherosclerosis and hence arterial disease, has recently been proffered as the main offender within the vascular system to predict not only the future onset of erectile dysfunction (ED) but also as the main cause of the ED. Reseachers reviewed the duplex ultrasound scans of 23 men with ED who were younger than 50 years of age. Depending on the criteria used for abnormal arterial responses, it was determined in this cohort of young men that there was only a 4–13% incidence of abnormal arterial responses.
These observations suggest that the penile arterial system does not appear to be primarily involved in the etiology of the majority cases of ED that occur in young men.
References:
1-Expand+British Journal of Anaesthesiabja.oxfordjournals.org Br. J. Anaesth. (2004) 93 (1): 105-113. doi: 10.1093/bja/aeh163 First published online: April 30, 2004
Physiology of the endothelium
H. F. Galley and N. R. Webster* Academic Unit of Anaesthesia & Intensive Care, School of Medicine, University of Aberdeen AB25 2ZD, Scotland UK
2-Wikipedia,The Free Encyclopedia 20 March 2013
3- International Journal of Impotence Research , (11 April 2013) | doi:10.1038/ijir.2013.17
Early onset erectile dysfunction is usually not associated with abnormal cavernosal arterial Inflow J Rajfer, J Valeriano and R Sinow
4- Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction
Fina Lovren1 and Subodh Verma1,2,*1 Division of Cardiac Surgery, Keenan Research Centre in the Li Ka Shing Knowledge Institute at St. Michael’s Hospital, 2 Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada. © 2013 The American Association for Clinical Chemistry
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