Thrombin-induced endothelial barrier disruption in intact microvessels: role of RhoA/Rho kinase-myosin phosphatase axis - PubMed (original) (raw)

. 2008 May;294(5):C1234-41.

doi: 10.1152/ajpcell.00551.2007. Epub 2008 Mar 19.

Affiliations

• PMID: 18353893
• DOI: 10.1152/ajpcell.00551.2007

Free article

Thrombin-induced endothelial barrier disruption in intact microvessels: role of RhoA/Rho kinase-myosin phosphatase axis

G P van Nieuw Amerongen et al. Am J Physiol Cell Physiol. 2008 May.

Free article

Abstract

Endothelial hyperpermeability is regulated by a myosin light chain-2 (MLC2) phosphorylation-dependent contractile mechanism. Thrombin is a potent inducer of hyperpermeability of cultured monolayers of endothelial cells (ECs) via Rho kinase-mediated MLC2-phosphorylation. The aim of the present study was to investigate the effects of thrombin on in situ endothelial morphology and barrier integrity. Cytoskeletal dynamics, regions of paracellular flux, and MLC2-phosphorylation of ECs were visualized by digital three-dimensional imaging microscopy of pressurized rat kidney arterioles. Myosin phosphatase targeting subunit (MYPT1)-phosphorylation was used as a surrogate marker for Rho kinase activity. Thrombin induced the formation of F-actin filaments in ECs in situ and rounding of the ECs in the absence of obvious formation of gaps between ECs. These changes were accompanied by an increase in MLC2 phosphorylation and a decrease in barrier integrity. In vitro analysis revealed that Rho kinase activity on F-actin filaments was associated with a contractile response that enhanced opening of the barrier. Rho kinase activity was not detectable on F-actin filaments induced by histamine, an inducer of a more transient hyperpermeability response. Inhibition of the myosin phosphatase mimicked the effects of thrombin on barrier function. The thrombin-induced changes in in situ MLC2 phosphorylation and barrier function were Rho kinase dependent. These data demonstrate a direct effect of thrombin on EC morphology and barrier integrity in intact microvessels. Furthermore, they establish an important contribution of enhanced Rho kinase activity to the development of prolonged but not transient types of endothelial barrier dysfunction.

PubMed Disclaimer

Similar articles

• cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling pathway.
  Aburima A, Wraith KS, Raslan Z, Law R, Magwenzi S, Naseem KM. Aburima A, et al. Blood. 2013 Nov 14;122(20):3533-45. doi: 10.1182/blood-2013-03-487850. Epub 2013 Oct 7. Blood. 2013. PMID: 24100445
• Activation of RhoA by thrombin in endothelial hyperpermeability: role of Rho kinase and protein tyrosine kinases.
  van Nieuw Amerongen GP, van Delft S, Vermeer MA, Collard JG, van Hinsbergh VW. van Nieuw Amerongen GP, et al. Circ Res. 2000 Aug 18;87(4):335-40. doi: 10.1161/01.res.87.4.335. Circ Res. 2000. PMID: 10948069
• Role of RhoA and Rho kinase in lysophosphatidic acid-induced endothelial barrier dysfunction.
  van Nieuw Amerongen GP, Vermeer MA, van Hinsbergh VW. van Nieuw Amerongen GP, et al. Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):E127-33. doi: 10.1161/01.atv.20.12.e127. Arterioscler Thromb Vasc Biol. 2000. PMID: 11116077
• The role of RhoA and Rho-associated kinase in vascular smooth muscle contraction.
  Swärd K, Mita M, Wilson DP, Deng JT, Susnjar M, Walsh MP. Swärd K, et al. Curr Hypertens Rep. 2003 Feb;5(1):66-72. doi: 10.1007/s11906-003-0013-1. Curr Hypertens Rep. 2003. PMID: 12530938 Review.
• Intracellular signalling involved in modulating human endothelial barrier function.
  van Hinsbergh VW, van Nieuw Amerongen GP. van Hinsbergh VW, et al. J Anat. 2002 Jun;200(6):549-60. doi: 10.1046/j.1469-7580.2002.00060.x. J Anat. 2002. PMID: 12162723 Free PMC article. Review.

Cited by

• The Vitamin K-Dependent Anticoagulant Factor, Protein S, Regulates Vascular Permeability.
  Joussaume A, Kanthou C, Pardo OE, Karayan-Tapon L, Benzakour O, Dkhissi F. Joussaume A, et al. Curr Issues Mol Biol. 2024 Apr 9;46(4):3278-3293. doi: 10.3390/cimb46040205. Curr Issues Mol Biol. 2024. PMID: 38666935 Free PMC article.
• Neurotensin modulates ovarian vascular permeability via adherens junctions.
  Pearson AC, Shrestha K, Curry TE Jr, Duffy DM. Pearson AC, et al. FASEB J. 2024 Apr 15;38(7):e23602. doi: 10.1096/fj.202302652RR. FASEB J. 2024. PMID: 38581236
• Diosmetin alleviates acute lung injury caused by lipopolysaccharide by targeting barrier function.
  Xia J, Li J, Deng M, Yin F, Liu J, Wang J. Xia J, et al. Inflammopharmacology. 2023 Aug;31(4):2037-2047. doi: 10.1007/s10787-023-01228-7. Epub 2023 Apr 19. Inflammopharmacology. 2023. PMID: 37074600 Free PMC article.
• Antithrombin-III mitigates thrombin-mediated endothelial cell contraction and sickle red blood cell adhesion in microscale flow.
  Wulftange WJ, Kucukal E, Man Y, An R, Monchamp K, Sevrain CD, Dashora HR, Owusu-Ansah AT, Bode A, Ilich A, Little JA, Key NS, Gurkan UA. Wulftange WJ, et al. Br J Haematol. 2022 Sep;198(5):893-902. doi: 10.1111/bjh.18328. Epub 2022 Jul 13. Br J Haematol. 2022. PMID: 35822297 Free PMC article.
• Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.
  Mostovenko E, Dahm MM, Schubauer-Berigan MK, Eye T, Erdely A, Young TL, Campen MJ, Ottens AK. Mostovenko E, et al. Part Fibre Toxicol. 2021 Oct 28;18(1):39. doi: 10.1186/s12989-021-00431-0. Part Fibre Toxicol. 2021. PMID: 34711247 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon

• Other Literature Sources

  • The Lens - Patent Citations