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World Sleep 2017, Prague, Czech Public
Oct 10
Poster Presentation
Kuang-Yu Chen 陳光裕
Poh-Ai Hospital, Taiwn

  Both of endothelialium and epithelium have their extracellular matrix (ECM), and ECM hardness would affect the airway smooth muscle (ASM), pulmonary vascular hyperplasia or proliferofibrosis, and affect the innate immunity even through activation of dendritic cells under focal inflammation stress.(Ref 1, 7)  





  
  VEGF Receptor (VEGFR) and integrins, Annexin-A2,PAR-1 were microstructures at cell surface to react through existence or concentration changes of ECM fibrinectin. Such as the perception of interstitial stiffness, the focal hypoxia from inflammation stress might introduce release or secretion of VEGF to the intracellular enviroment of the stem cells, or even introduce the ECM innate immune system that are originally situated to react to initiate the subsequent reaction of the ERK message to the downstreamed messages chains. (Ref 5, 6)

  When the physiological enviroment in sleep breathing disorder, e.g upper airway collapse in OSA with high loop gain or low airway bronchospasm hypoxia developed to produce a focal interstitium that suddenly was irrigated with the reactive and excessive VEGF and their type 2 receptors also massively appear. Current data revealed endothelial cells under stretching and low ECM stiffness would change the intracellular electro- and chemical transfer system to further enforce the cells with ability to produce VEGF receptor type 2 to bind VEGF with more effectiveness in hypoxia matrix, with a consequence the whole system can be more intense to "capture" more VEGF from ECM. (Ref 2)


  When the ECM hardness is getting high and through accumulation of thrombin, Factor Xa (FXa) or other coagulation-related factors, the angiogenesis will accelerate, but, it would also have effect on the ECM stiffness. Dependent to the condition of extracellular MMP-3 production as a protein decomposition factor existance, that you can think of a car gearbox or train trajectory switch, then the impact of VEGF-CTGF linkages those were supposed through the Rho-A message chains would lead to neovascular endothelium formation, or would lead to the different pathway of myofibroblasts production. 

In summary, the effect of VEGF-integrins would become more potent in order to consolidate the local cell tissue survival opportunities. The more hardened and thicker extracellular matrix under hypoxia due to both upper and lower airway physical stretching, the more angiogenesis would be found through VEGF/VEGFR and thrombin interaction. 

References:

  1. Maria Kechagia et al Endocan and the respiratory system: a review Int J Chron Obstruct Pulmon Dis. 2016; 11: 3179–3187 doi:  10.2147/COPD.S118692
  2. Simons M et al Mechanisms and regulation of endothelial VEGF receptor signaling Nat Rev Mol Cell Biol. 2016 Oct;17(10):611-625 doi: 10.1038/nrm.2016.87. Epub 2016 Jul 27. 
  3. Anne Briancon-Marjollet et al Intermittent hypoxia upregulates serum VEGF　Letters to the Editor Sleep Medicine  2014;15 :1424-1429
  4. Christos A. Goudis and Dimitrios G. Ketikoglou Obstructive sleep and atrial fibrillation: Pathophysiological mechanisms and therapeutic implications International Journal of Cardiology 2017;230:293–300 http://dx.doi.org/10.1016/j.ijcard.2016.12.120
  5. Kelsey D. Sack et al Extracellular Matrix Stiffness Controls VEGF Signaling and Processing in Endothelial Cells J Cell Physiol  2016;231: 2026-2039
  6. Changjun Li et al RhoA determines lineage fate of mesenchymal stem cells by modulating CTGF–VEGF complex in extracellular matrix Nature Communication 2016;7:11455  DOI: 10.1038/ncomms11455
  7. Janette K Burgess et al The extracellular matrix – the under-recognized element in lung disease? J Pathol 2016; 240: 397–409 DOI: 10.1002/path.4808



My blog in Chinese/mandarin 
硬不硬，有關係之 VEGF血管內皮生長因子的致病之旅。



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