vascular disease Vascular disease is a class of diseases of the blood vessels – the arteries and veins of the circulatory system of the body. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood vessels can cause a ra ...

s, endothelial dysfunction is a systemic pathological state of the

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining

vascular tone Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be ca ...

and regulating oxidative stress by releasing mediators, such as

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

, prostacyclin and endothelin, and controlling local angiotensin-II activity.

Research

Atherosclerosis

Endothelial dysfunction may be involved in the development of atherosclerosis and may predate vascular pathology. Endothelial dysfunction can also lead to increased adherence of

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

s and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s, as well as promoting infiltration of

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

in the vessel wall. Dyslipidemia and

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

are well known to contribute to endothelial dysfunction, and lowering blood pressure and LDL has been shown to improve endothelial function, particularly when lowered with

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

s, and statins.

Nitric oxide

Nitric oxide (NO) suppresses platelet aggregation, inflammation, oxidative stress, vascular smooth muscle cell migration and proliferation, and leukocyte adhesion. A feature of endothelial dysfunction is the inability of arteries and

arterioles An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have muscular walls (usually only one to two layers of smooth muscle cells) and are the primar ...

to dilate fully in response to an appropriate stimulus, such as

exogenous In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. Economics In an economic model, an exogeno ...

nitroglycerine, 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 or inactivation of NO by reactive

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

species.

Testing and diagnosis

In the

coronary circulation Coronary circulation is the circulation of blood in the blood vessels that supply the heart muscle (myocardium). Coronary arteries supply oxygenated blood to the heart muscle. Cardiac veins then drain away the blood after it has been deoxygenat ...

, angiography of

coronary artery The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...

responses to vasoactive agents may be used to test for endothelial function, and venous occlusion

plethysmography A plethysmograph is an instrument for measuring changes in volume within an organ or whole body (usually resulting from fluctuations in the amount of blood or air it contains). The word is derived from the Greek "plethysmos" (increasing, enla ...

and

ultrasonography Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

are used to assess endothelial function of peripheral vessels in humans. A non-invasive method to measure endothelial dysfunction is %

Flow-Mediated Dilation Flow-mediated dilation (FMD) refers to dilation (widening) of an artery when blood flow increases in that artery. The primary cause of FMD is release of nitric oxide by endothelial cells. To determine FMD, brachial artery dilation following a tran ...

(FMD) as measured by Brachial Artery Ultrasound Imaging (BAUI). Current measurements of endothelial function via FMD vary due to technical and physiological factors. Furthermore, a negative correlation between percent flow mediated dilation and baseline artery size is recognised as a fundamental scaling problem, leading to biased estimates of endothelial function. A non-invasive,

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

-approved device for measuring endothelial function that works by measuring Reactive Hyperemia Index (RHI) is

Itamar Medical Itamar Medical is a multinational company focused on the development, manufacturing and sales of medical devices related to respiratory sleep disorders. The company is headquartered in Caesarea, Israel and is owned by ZOLL Medical Corporation. T ...

’s EndoPAT. It has shown an 80% sensitivity and 86% specificity to diagnose

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

when compared against the gold standard, acetylcholine angiogram. This results suggests that this peripheral test reflects the physiology of the coronary endothelium. Since NO maintains low tone and high compliance of the small arteries at rest, a reduction of age-dependent small artery compliance is a marker for endothelial dysfunction that is associated with both functional and structural changes in the microcirculation. Small artery compliance or stiffness can be assessed simply and at rest and can be distinguished from large artery stiffness by use of pulsewave analysis.

Endothelial dysfunction and stents

Stent implantation has been correlated with impaired endothelial function in several studies. Sirolimus eluting stents were previously used because they showed low rates of in-stent restenosis, but further investigation showed that they often impair endothelial function in humans and worsen conditions. One drug used to inhibit restenosis is

iopromide Iopromide is an iodinated contrast medium for X-ray imaging. It is marketed under the name Ultravist which is produced by Bayer Healthcare. It is a low osmolar, non-ionic contrast agent for intravascular use; i.e., it is injected into blood vesse ...

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...

Risk reduction

Treatment of

and hypercholesterolemia may improve endothelial function in people taking

statins Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...

(HMGCoA-reductase inhibitor), and

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

angiotensin system inhibitors, such as ACE inhibitors and

angiotensin II receptor antagonists Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

. Calcium channel blockers and selective beta 1 antagonists may also improve endothelial dysfunction. Life style modifications such as smoking cessation have also been shown to improve endothelial function and lower the risk of major cardiovascular events.

References

{{reflist, colwidth=30em Vascular diseases