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 ...

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 vesse ...

. Along with acting as a

semi-permeable membrane Semipermeable membrane is a type of biological or synthetic, polymeric membrane that will allow certain molecules or ions to pass through it by osmosis. The rate of passage depends on the pressure, concentration, and temperature of the molecule ...

, 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 Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...

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 Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosteno ...

and

endothelin Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute ...

, and controlling local

angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adren ...

-II activity.

Research

Atherosclerosis

Endothelial dysfunction may be involved in the development of

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

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 ...

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 Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary ar ...

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

statin 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 ...

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 An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...

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 Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating ...

, that stimulates release of

vasodilators Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...

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 Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfor ...

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 ...

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, enlar ...

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 A medical procedure is defined as ''non-invasive'' when no break in the skin is created and there is no contact with the mucosa, or skin break, or internal body cavity beyond a natural or artificial body orifice. For example, deep palpation and p ...

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 ...

(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 ...

-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 Coronary () may, as shorthand in English, be used to mean: * Coronary circulation, the system of arteries and veins in mammals ** Coronary artery disease **Coronary occlusion ** A myocardial infarction, a heart attack As adjective * Referring to ...

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 In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandab ...

implantation has been correlated with impaired endothelial function in several studies.

Sirolimus Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosi ...

eluting stents were previously used because they showed low rates of in-stent

restenosis Restenosis is the recurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow. Restenosis usually pertains to an artery or other large blood vessel that has become narrowed, received treatment to clear the blockage and s ...

, but further investigation showed that they often impair endothelial function in humans and worsen conditions. One drug used to inhibit restenosis is iopromide-

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 canc ...

Risk reduction

Treatment of

and

hypercholesterolemia Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...

may improve endothelial function in people taking statins (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 ...

system inhibitors, such as

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

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