Endothelial activation

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Endothelial activation is a proinflammatory and procoagulant state of the endothelial cells lining the lumen of blood vessels. [1] It is most characterized by an increase in interactions with white blood cells (leukocytes), and it is associated with the early states of atherosclerosis and sepsis, among others. [2] It is also implicated in the formation of deep vein thrombosis. [3] As a result of activation, enthothelium releases Weibel–Palade bodies. [4]

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Mechanical sensing and responses

Elevating shear stress induces a vascular response by triggering nitric oxide synthesis and mechanotransduction pathways of endothelial cells. [5] The synthesis of nitric oxide facilitate shear stress mediated dilation in blood vessels and maintains a homeostatic status. [6] Additionally, physiologic shear stress levels at the vessel wall upregulate the presence of antithrombotic agents through the mechano-signal transduction of mechano-recepting transmembrane proteins, junctional proteins, and subendothelial mechanosensors. [7] Shear stress causes endothelial cell deformation which activates transmembrane ion channels [8] Elevated wall shear stress caused by exercise is understood to promote mitochondrial biogenesis in the vascular endothelium indicating the benefits regular exercise may have on vascular function. [9] Alignment is recognized as an important mechanism and determinant of shear-stress induced vascular response; in vivo testing of endothelial cells has demonstrated that their mechanotransductive response is direction dependent as endothelial nitric oxide synthesis is preferentially activated under parallel flow while perpendicular flows activates inflammatory pathways like reactive oxygen species production and nuclear factor-κB. [10] Therefore, disturbed/oscillating flow and low flow conditions, which create an irregular and passive shear stress environment, result in inflammatory activation due to a limited alignment capability of the endothelial cells. Regions in the vasculature with low shear stress are vulnerable to elevated monocyte adhesion and endothelial cell apoptosis. [11] However, unlike oscillatory flow, both laminar(steady) and pulsatile flow and shear stress environments are often considered together as mechanisms of maintaining vascular homeostasis and preventing inflammation, reactive oxygen species formation, and coagulatory pathways. [12] High, uniform laminar shear stress is known to promote a quiescent endothelial cell state, provide anti-thrombotic effects, prevent proliferation, and decrease inflammation and apoptosis. At high shear stress levels (10 Pa), the endothelial cell response is distinct from upper normal/physiological values; high wall shear stress causes a promatrix remodeling, proliferative, anticoagulant, and anti-inflammatory state. [13] Yet, very high wall shear stress values (28.4 Pa) prevent endothelial cell alignment and stimulate proliferation and apoptosis although the endothelial response to shear stress environments was determined to be dependent on the local wall shear stress gradient. [14]

See also

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References

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  2. ↑ Alom-Ruiz SP, Anilkumar N, Shah AM (June 2008). "Reactive oxygen species and endothelial activation". Antioxidants & Redox Signaling. 10 (6): 1089–100. doi:10.1089/ars.2007.2007. PMID   18315494.
  3. ↑ Bovill EG, van der Vliet A (2011). "Venous valvular stasis-associated hypoxia and thrombosis: what is the link?". Annual Review of Physiology. 73: 527–45. doi:10.1146/annurev-physiol-012110-142305. PMID   21034220.
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  5. ↑ Rodríguez I, González M (2014-09-16). "Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation". Frontiers in Pharmacology. 5: 209. doi: 10.3389/fphar.2014.00209 . PMC   4165280 . PMID   25278895.
  6. ↑ Lu D, Kassab GS (October 2011). "Role of shear stress and stretch in vascular mechanobiology". Journal of the Royal Society, Interface. 8 (63): 1379–85. doi:10.1098/rsif.2011.0177. PMC   3163429 . PMID   21733876.
  7. ↑ Papaioannou TG, Stefanadis C (January–February 2005). "Vascular wall shear stress: basic principles and methods". Hellenic Journal of Cardiology. 46 (1): 9–15. PMID   15807389.
  8. ↑ Lee J, Packard RR, Hsiai TK (October 2015). "Blood flow modulation of vascular dynamics". Current Opinion in Lipidology. 26 (5): 376–83. doi:10.1097/MOL.0000000000000218. PMC   4626080 . PMID   26218416.
  9. ↑ Kim B, Lee H, Kawata K, Park JY (2014). "Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium". PLOS ONE. 9 (11): e111409. Bibcode:2014PLoSO...9k1409K. doi: 10.1371/journal.pone.0111409 . PMC   4222908 . PMID   25375175.
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  11. ↑ Berk BC (February 2008). "Atheroprotective signaling mechanisms activated by steady laminar flow in endothelial cells". Circulation. 117 (8): 1082–9. doi: 10.1161/CIRCULATIONAHA.107.720730 . PMID   18299513.
  12. ↑ Hsieh HJ, Liu CA, Huang B, Tseng AH, Wang DL (January 2014). "Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications". Journal of Biomedical Science. 21 (1): 3. doi: 10.1186/1423-0127-21-3 . PMC   3898375 . PMID   24410814.
  13. ↑ Dolan JM, Sim FJ, Meng H, Kolega J (April 2012). "Endothelial cells express a unique transcriptional profile under very high wall shear stress known to induce expansive arterial remodeling". American Journal of Physiology. Cell Physiology. 302 (8): C1109-18. doi:10.1152/ajpcell.00369.2011. PMC   3330730 . PMID   22173868.
  14. ↑ Dolan JM, Meng H, Singh S, Paluch R, Kolega J (June 2011). "High fluid shear stress and spatial shear stress gradients affect endothelial proliferation, survival, and alignment". Annals of Biomedical Engineering. 39 (6): 1620–31. doi:10.1007/s10439-011-0267-8. PMC   4809045 . PMID   21312062.

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