alexa Role of phospholipase C, protein kinase C, and calcium in VEGF-induced venular hyperpermeability.


Journal of Pulmonary & Respiratory Medicine

Author(s): Wu HM, Yuan Y, Zawieja DC, Tinsley J, Granger HJ

Abstract Share this page

Abstract We previously demonstrated that vascular endothelial growth factor (VEGF)-elicited increase in the permeability of coronary venules was blocked by the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). The aim of this study was to delineate in more detail the signaling pathways upstream from NO production in VEGF-induced venular hyperpermeability. The apparent permeability coefficient of albumin (Pa) and endothelial cytosolic Ca2+ concentration ([Ca2+]i) were measured in intact perfused porcine coronary venules using fluorescence microscopy. VEGF (10(-10) M) induced a two- to threefold increase in Pa, which was blocked by a monoclonal antibody directed against the VEGF receptor Flk-1/KDR, the phospholipase C (PLC) antagonist U-73122, or the protein kinase C (PKC) antagonist bisindolylmaleimide (BIM). In 12 venules that displayed the [Ca2+]i response to bradykinin (10(-6) M) and ionomycin (10(-6) M), only 4 vessels responded to VEGF with a transient increase in [Ca2+]i. Furthermore, Western blot analysis of cultured human umbilical vein endothelial cells showed that VEGF increased tyrosine phosphorylation of PLC-gamma and serine phosphorylation of endothelial constitutive NO synthase (ecNOS). The hyperphosphorylation of PLC-gamma was greatly attenuated by the KDR receptor antibody and U-73122, but not by BIM or L-NMMA. In contrast, U-73122 and BIM were able to inhibit VEGF-elicited serine phosphorylation of ecNOS. The results suggest that VEGF induces venular hyperpermeability through a KDR receptor-mediated activation of PLC. In turn, ecNOS is activated by PLC-mediated PKC and/or cytosolic Ca2+ elevation stimulation.
This article was published in Am J Physiol and referenced in Journal of Pulmonary & Respiratory Medicine

Relevant Expert PPTs

Relevant Speaker PPTs

  • Shoude Jin
    Mechanisms of Chronic obstructive pulmonary disease and airway smooth muscle remodeling: the potential roles of Abhd2
    PDF Version
  • Alsayed Alnahal
    Urinary netrin-1 predict early ischemic acute kidney injury after cardiopulmonary bypass
    PPT Version | PDF Version
  • Ping Yang
    Chronic obstructive pulmonary disease (COPD) complicating early-stage lung cancer (LC)
    PDF Version
  • Gunilla Lindqvist
    Chronic obstructive pulmonary disease: A study of the relationship between patients’ feeling of guilt due to their belief of the disease being self inflicted
    PDF Version
  • Roger Mark Engel
    The effect of including manual therapy in the management of mild chronic obstructive pulmonary disease – a randomized controlled trial
    PDF Version
  • Rupal Patel Mansukhani
    Correlation of Medication Therapy in Chronic Obstructive Pulmonary Disease(COPD) Patients with 30-day Readmission Rates
    PPT Version | PDF Version
  • Hadeel Faisal Gad
    In-vitro analysis of cytokines responses of visceral leishmaniasis and pulmonary tuberculosis patients to homologous and heterologous antigen stimulation
    PPT Version | PDF Version
  • Xin Wang
    IL17 Pathway Involves Moderating Pulmonary Hypertension, a common complication of COPD, in Statins Therapy in Smoking Rats
    PPT Version | PDF Version

Recommended Conferences

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version