Endothelial dysfunction
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In
Dysfunctional endothelium is characterized by vasoconstriction, increased vascular permeability, thrombosis, and inflammation. This pathological state is often associated with elevated levels of biomarkers such as prothrombin time, D-dimer, fibrin degradation products, C-reactive protein (CRP), ferritin, Interleukin 6 (IL-6), and plasma creatinine. The result of this endothelial dysregulation is a cascade of adverse effects, including vasoconstriction, vascular leakage, thrombosis, hyperinflammation, and a disrupted antiviral immune response. These changes contribute to the progression of vascular diseases.[3]
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]
Research
Atherosclerosis
Endothelial dysfunction may be involved in the development of atherosclerosis[4][5][6] and may predate vascular pathology.[4][7] Endothelial dysfunction may also lead to increased adherence of monocytes and macrophages, as well as promoting infiltration of low-density lipoprotein (LDL) in the vessel wall.[8] Dyslipidemia and hypertension are well known to contribute to endothelial dysfunction,[9][10] and lowering blood pressure and LDL has been shown to improve endothelial function, particularly when lowered with ACE inhibitors, calcium channel blockers, and statins.[11]
Nitric oxide
Nitric oxide (NO) suppresses platelet aggregation, inflammation, oxidative stress, vascular smooth muscle cell migration and proliferation, and leukocyte adhesion.
Testing and diagnosis
In the
A
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
See also
- Atherosclerosis
- Endothelial activation
- Nitric oxide
- endothelial nitric oxide synthase
- Prostacyclin
- Endothelium-derived relaxing factor
- Endothelin
- Integrin network
- Endothelial shear stress
References
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