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Endothelial dysfunction

In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress by releasing mediators, such as nitric oxide, prostacyclin and endothelin, and controlling local angiotensin-II activity.[1][2]

Contents

ResearchEdit

AtherosclerosisEdit

Endothelial dysfunction may be involved in the development of atherosclerosis[3][4] and may predate vascular pathology.[3][5]

Nitric oxideEdit

Nitric oxide (NO) suppresses platelet aggregation, inflammation, oxidative stress, vascular smooth muscle cell migration and proliferation, and leukocyte adhesion.[4] A feature of endothelial dysfunction is the inability of arteries and arterioles to dilate fully in response to an appropriate stimulus, such as exogenous nitroglycerine,[3] 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]

Testing and diagnosisEdit

In the coronary circulation, angiography of coronary artery responses to vasoactive agents may be used to test for endothelial function, and venous occlusion plethysmography and ultrasonography are used to assess endothelial function of peripheral vessels in humans.[3]

A non-invasive method to measure endothelial dysfunction is % Flow-Mediated Dilation (FMD) as measured by Brachial Artery Ultrasound Imaging (BAUI).[6] 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.[7]

A non-invasive, FDA-approved device for measuring endothelial function that works by measuring Reactive Hyperemia Index (RHI) is Itamar Medical's EndoPAT™.[8][9] It has shown an 80% sensitivity and 86% specificity to diagnose coronary artery disease when compared against the gold standard, acetylcholine angiogram.[10] 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,[11] 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.[12] 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.[13]

Endothelial dysfunction and stentsEdit

Stent implantation has been correlated with impaired endothelial function in several studies.[14] 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.[14] One drug used to inhibit restenosis is iopromide-paclitaxel.[15]

Risk reductionEdit

Treatment of hypertension and hypercholesterolemia may improve endothelial function in people taking statins (HMGCoA-reductase inhibitor), and renin angiotensin system inhibitors, such as ACE inhibitors and angiotensin II receptor antagonists.[16][17]

See alsoEdit

Relevant endothelial function molecular mediators:

Relevant endothelial function molecular pathways:

Relevant biophysical endothelial function mediators:

ReferencesEdit

  1. ^ Sitia, S.; Tomasoni, L.; Atzeni, F.; Ambrosio, G.; Cordiano, C.; Catapano, A.; Tramontana, S.; Perticone, F.; Naccarato, P. (2010). "From endothelial dysfunction to atherosclerosis". Autoimmunity Reviews. 9 (12): 830–834. doi:10.1016/j.autrev.2010.07.016. PMID 20678595.
  2. ^ Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Lüscher TF, Shechter M, Taddei S, Vita JA, Lerman A (Aug 2012). "The assessment of endothelial function: from research into clinical practice". Circulation. 126 (6): 753–67. doi:10.1161/circulationaha.112.093245. PMC 3427943. PMID 22869857.
  3. ^ a b c d Maruhashi, T; Kihara, Y; Higashi, Y (2018). "Assessment of endothelium-independent vasodilation: From methodology to clinical perspectives". Journal of Hypertension. 36 (7): 1460–1467. doi:10.1097/HJH.0000000000001750. PMID 29664811.
  4. ^ a b Eren E, Yilmaz N, Aydin O (2013). "Functionally defective high-density lipoprotein and paraoxonase: a couple for endothelial dysfunction in atherosclerosis". Cholesterol. 2013: 1–10. doi:10.1155/2013/792090. PMC 3814057. PMID 24222847.
  5. ^ Münzel T, Sinning C, Post F, Warnholtz A, Schulz E (2008). "Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction". Annals of Medicine. 40 (3): 180–96. doi:10.1080/07853890701854702. PMID 18382884.
  6. ^ Peretz, Alon; Daniel F Leotta; Jeffrey H Sullivan; Carol A Trenga; Fiona N Sands; Mary R Aulet (2007). "Flow mediated dilation of the brachial artery: an investigation of methods requiring further standardization". BMC Cardiovascular Disorders. 7 (11): 11. doi:10.1186/1471-2261-7-11. PMC 1847451. PMID 17376239.
  7. ^ Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ (Jan 2011). "Assessment of flow-mediated dilation in humans: a methodological and physiological guideline". Am J Physiol Heart Circ Physiol. 300 (1): H2–12. doi:10.1152/ajpheart.00471.2010. PMC 3023245. PMID 20952670.
  8. ^ Kuvin JT, Mammen A, Mooney P, Alsheikh-Ali AA, Karas RH (Feb 2007). "Assessment of peripheral vascular endothelial function in the ambulatory setting". Vasc. Med. 12 (1): 13–6. doi:10.1177/1358863x06076227. PMID 17451088.
  9. ^ Axtell AL, Gomari FA, Cooke JP (October 2010). "Assessing endothelial vasodilator function with the Endo-PAT 2000". Journal of Visualized Experiments : JoVE (44). doi:10.3791/2167. PMC 3143035. PMID 20972417.
  10. ^ Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A (Dec 2004). "Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia". J Am Coll Cardiol. 44 (11): 2137–41. doi:10.1016/j.jacc.2004.08.062. PMID 15582310.
  11. ^ 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. PMID 20409832.
  12. ^ Duprez DA, Jacobs DR, Lutsey PL, Bluemke FA, Brumback LC, Polak JF, Peralta CA, Greenland P, Kronmal RA (2011). "Association of small artery elasticity with incident cardiovascular disease in older adults: the multiethnic study of atherosclerosis". Am J Epidemiol. 174 (5): 528–36. doi:10.1093/aje/kwr120. PMC 3202150. PMID 21709134.
  13. ^ Cohn JN, Duprez DA, Finkelstein SM (2009). "Comprehensive noninvasive arterial vascular evaluation". Future Cardiology. 5 (6): 573–9. doi:10.2217/fca.09.44. PMID 19886784.
  14. ^ a b Bedair, T. M; Elnaggar, M. A; Joung, Y. K; Han, D. K (2017). "Recent advances to accelerate re-endothelialization for vascular stents". Journal of Tissue Engineering. 8: 2041731417731546. doi:10.1177/2041731417731546. PMC 5624345. PMID 28989698.
  15. ^ Unverdorben, Martin; Vallbracht, Christian; Cremers, Bodo; Heuer, Hubertus; Hengstenberg, Christian; Maikowski, Christian; Werner, Gerald S.; Antoni, Diethmar; Kleber, Franz X. (2009-06-16). "Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis". Circulation. 119 (23): 2986–2994. doi:10.1161/circulationaha.108.839282. ISSN 0009-7322. PMID 19487593.
  16. ^ Ruilope LM, Redón J, Schmieder R (2007). "Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors, or both? Expectations from the ONTARGET Trial Programme". Vascular Health and Risk Management. 3 (1): 1–9. PMC 1994043. PMID 17583170.
  17. ^ 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. PMID 22280336.