In a healthy state, the endothelium exhibits
vasodilation, tightly controlled vascular permeability, and anti-thrombotic and anti-inflammatory properties. This balance ensures the smooth functioning of the vascular system.[3]
Nitric oxide (NO) suppresses platelet aggregation, inflammation, oxidative stress, vascular smooth muscle cell migration and proliferation, and leukocyte adhesion.[5] A feature of endothelial dysfunction is the inability of
arteries and
arterioles to dilate fully in response to an appropriate stimulus, such as
exogenousnitroglycerine,[4] 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 species.[citation needed]
A
non-invasive method to measure endothelial dysfunction is %
Flow-Mediated Dilation (FMD) as measured by Brachial Artery Ultrasound Imaging (BAUI).[12] 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.[13]
A non-invasive,
FDA-approved device for measuring endothelial function that works by measuring
Reactive Hyperemia Index (RHI) is
Itamar Medical's EndoPAT.[14][15] It has shown an 80% sensitivity and 86% specificity to diagnose
coronary artery disease when compared against the gold standard, acetylcholine angiogram.[16] 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,[17] 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.[18] 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.[19]
Endothelial dysfunction and stents
Stent implantation has been correlated with impaired endothelial function in several studies.[20]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.[20] One drug used to inhibit restenosis is
iopromide-
paclitaxel.[21]
Risk reduction
Treatment of
hypertension and
hypercholesterolemia may improve endothelial function in people taking
statins (HMGCoA-reductase inhibitor), and
reninangiotensin system inhibitors, such as
ACE inhibitors and
angiotensin II receptor antagonists.[22][23] Calcium channel blockers and selective beta 1 antagonists may also improve endothelial dysfunction.[11] Life style modifications such as smoking cessation have also been shown to improve endothelial function and lower the risk of major cardiovascular events.[24]
^Gilani M, Kaiser DR, Bratteli CW, Alinder C, Rajala Bank AJ, Cohn JN (2007). "Role of nitric oxide deficiency and its detection as a risk factor in pre-hypertension". JASH. 1 (1): 45–56.
doi:
10.1016/j.jash.2006.11.002.
PMID20409832.
^Briasoulis A, Tousoulis D, Androulakis ES, Papageorgiou N, Latsios G, Stefanadis C (Apr 2012). "Endothelial dysfunction and atherosclerosis: focus on novel therapeutic approaches". Recent Pat Cardiovasc Drug Discov. 7 (1): 21–32.
doi:
10.2174/157489012799362386.
PMID22280336.