Effect of Factor XIII on Endothelial Barrier Function

Noll, Thomas; Wozniak, Gernold; McCarson, Kenneth E.; Hajimohammad, Amir; Metzner, Hubert J.; Inserte, Javier; Kummer, Wolfgang; Hehrlein, F. W.; Piper, Hans Michael

doi:10.1084/jem.189.9.1373

Cited by 66 publications

(63 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…19 In this model, insulin caused a strong reduction of the reperfusion-induced increase in myocardial water content if applied for only a short period of time during the early phase of reperfusion. These data indicate that insulin is also a potent stabilizer of the vascular permeability barrier in the intact coronary system and that its application during reperfusion can protect the heart against an imminent edema.…”

Section: Gü Ndü Z Et Almentioning

confidence: 99%

Insulin Stabilizes Microvascular Endothelial Barrier Function via Phosphatidylinositol 3-Kinase/Akt-Mediated Rac1 Activation

Gündüz

Thom

Hussain

et al. 2010

ATVB

Self Cite

View full text Add to dashboard Cite

Objective-Insulin is a key regulator of metabolism, but it also confers protective effects on the cardiovascular system.Here, we analyze the mechanism by which insulin stabilizes endothelial barrier function. Methods and Results-Insulin reduced basal and antagonized tumor necrosis factor-␣-induced macromolecule permeability of rat coronary microvascular endothelial monolayers. It also abolished reperfusion-induced vascular leakage in isolated-perfused rat hearts. Insulin induced dephosphorylation of the regulatory myosin light chains, as well as translocation of actin and vascular endothelial (VE)-cadherin to cell borders, indicating a reduction in contractile activation and stabilization of cell adhesion structures. These protective effects were blocked by genistein or Hydroxy-2-naphthalenylmethylphosphonic acid tris acetoxymethyl ester (HNMPA-[AM] 3 ), a pan-tyrosine-kinase or specific insulin-receptor-kinase inhibitor, respectively. Insulin stimulated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and NO production, and it activated Rac1. Inhibition of PI3K/Akt abrogated Rac1 activation and insulin-induced barrier protection, whereas inhibition of the endothelial nitric oxide synthase/soluble guanylyl cyclase pathway partially inhibited them. Inhibition of Rac1 abrogated the assembly of actin at cell borders. Accordingly, it abolished the protective effect of insulin on barrier function of the cultured endothelial monolayer, as well as the intact coronary system of ischemic-reperfused hearts. Key Words: capillary permeability Ⅲ coronary circulation Ⅲ endothelium Ⅲ nitric oxide Ⅲ vascular biology I nsulin is an essential hormone of metabolic homeostasis. Recent clinical findings show that intensive insulin therapy has vasoprotective effects under inflammatory conditions 1,2 and reduces major cardiovascular events in diabetics. 3 These effects of insulin seem to be independent of its metabolic effects on endothelial cells. Conclusion-InsulinVascular endothelial cells forming the inner lining of all vessels play an important role in the regulation of vascular homeostasis. They provide a semiselective barrier for water, solutes, macromolecules, and blood-borne components and are also involved in regulating the trafficking of blood cells across the vessel wall. This function can be altered by a variety of diverse circulating vasoactive inflammatory mediators and hormones such as insulin. It has recently been demonstrated that endothelial cells of macrovascular origin express insulin receptors. 4 Binding of insulin to the receptors induces nitric oxide production via phosphatidylinositol 3-kinase (PI3K)-mediated activation of endothelial nitric oxide synthase (eNOS) 5 and causes relaxation of the smooth muscles. Recently, it has been shown that insulin reduces mesenteric venular albumin leakage on systemic insulin administration in rats. 6 However, the underlying signaling mechanism of this effect is largely unknown.The integrity of the endothelial barrier is highly dependent on the endothelial actomyosi...

show abstract

Section: Gü Ndü Z Et Almentioning

confidence: 99%

Insulin Stabilizes Microvascular Endothelial Barrier Function via Phosphatidylinositol 3-Kinase/Akt-Mediated Rac1 Activation

Gündüz

Thom

Hussain

et al. 2010

ATVB

Self Cite

View full text Add to dashboard Cite

show abstract

“…Factor XIII has a role in endothelial barrier function (145), reducing endothelial permeability, apparently by modifying paracellular transport in endothelial cell monolayers. In an animal model, factor XIII blocked enhanced permeability induced by antiendothelial cell antiserum (146).…”

Section: Role Of Transglutaminases In Vascular Permeabilitymentioning

confidence: 99%

Roles of transglutaminases in cardiac and vascular diseases

Sane

Kontos²,

Greenberg³

2007

Front Biosci

View full text Add to dashboard Cite

All transglutaminases share the common enzymatic activity of transamidation, or the cross-linking of glutamine and lysine residues to form N epsilon (gamma-glutamyl) lysyl isopeptide bonds. The plasma proenzyme factor XIII is responsible for stabilizing the fibrin clot against physical and fibrinolytic disruption. Another member of the transglutaminase family, tissue transglutaminase or TG2 is abundantly expressed in cardiomyocytes, vascular cells and macrophages. The transglutaminases have a variety of functions independent of their transamidating activity. For example, TG2 binds and hydrolyzes GTP, thereby fostering signal transduction by several G protein coupled receptors. Accumulating evidence points to novel roles for factor XIII and TG2 in cardiovascular biology including: (a) modulating platelet activity, (b) regulating glucose control, (c) contributing to the development of hypertension, (d) influencing the progression of atherosclerosis, (e) regulating vascular permeability and angiogenesis (f) and contributing to myocardial signaling, contractile activity and ischemia/reperfusion injury. In this review, we summarize the cardiovascular biology of two members of the family of transglutaminases, Factor XIII and TG2.

show abstract

“…The permeability of Trypan blue-labeled albumin across human lung blood microvascular endothelial cell (HMVEC-L) monolayers was studied in a two-compartment system separated by a filter membrane as described previously (28). Both compartments contained as basal medium modified Tyrode solution (composition in mM: 150 NaCl, 2.7 KCl, 1.2 KH 2PO4, 1.2 MgSO4, 1.0 CaCl2, and 30.0 N-2-hydroxyethylpiperazine-NЈ-2-ethanesulfonic acid; pH 7.4, 37°C) supplemented with 2% (vol/vol) normal calf serum.…”

Section: Animalsmentioning

confidence: 99%

Intermedin/adrenomedullin-2 is a hypoxia-induced endothelial peptide that stabilizes pulmonary microvascular permeability

Pfeil¹,

Aslam

Paddenberg³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

Weissmann N, Kummer W. Intermedin/adrenomedullin-2 is a hypoxia-induced endothelial peptide that stabilizes pulmonary microvascular permeability. Am J Physiol Lung Cell Mol Physiol 297: L837-L845, 2009. First published August 14, 2009 doi:10.1152/ajplung.90608.2008.-Accumulating evidence suggests a pivotal role of the calcitonin receptor-like receptor (CRLR) signaling pathway in preventing damage of the lung by stabilizing pulmonary barrier function. Intermedin (IMD), also termed adrenomedullin-2, is the most recently identified peptide targeting this receptor. Here we investigated the effect of hypoxia on the expression of IMD in the murine lung and cultured murine pulmonary microvascular endothelial cells (PMEC) as well as the role of IMD in regulating vascular permeability. Monoclonal IMD antibodies were generated, and transcript levels were assayed by quantitative RT-PCR. The promoter region of IMD gene was analyzed, and the effect of hypoxia-inducible factor (HIF)-1␣ on IMD expression was investigated in HEK293T cells. Isolated murine lungs and a human lung microvascular endothelial cell monolayer model were used to study the effect of IMD on vascular permeability. IMD was identified as a pulmonary endothelial peptide by immunohistochemistry and RT-PCR. Hypoxia caused an upregulation of IMD mRNA in the murine lung and PMEC. As shown by these results, HIF-1␣ enhances IMD promoter activity. Our functional studies showed that IMD abolished the increase in pressure-induced endothelial permeability. Moreover, IMD decreased basal and thrombin-induced hyperpermeability of an endothelial cell monolayer in a receptor-dependent manner and activated PKA in these cells. In conclusion, IMD is a novel hypoxiainduced gene and a potential interventional agent for the improvement of endothelial barrier function in systemic inflammatory responses and hypoxia-induced vascular leakage. endothelial permeability; edema THE PULMONARY VASCULAR ENDOTHELIUM forms a continuous, semipermeable dynamic barrier for water, solutes, and plasma proteins between the intravascular space and underlying tissues. Impairment of the barrier function results in vascular leakage and pulmonary edema formation. Inflammatory cytokines (22, 36), viruses (17, 30), biophysical forces such as stretch and shear stress (25,29), and hypoxia (3, 7, 27, 40) can lead to increased endothelial cell permeability, thus disrupting the segregation between blood plasma and interstitial fluid. Accumulating evidence suggests a pivotal role of the calcitonin receptor-like receptor (CRLR) signaling pathway in stabilizing this barrier function and preventing pulmonary damage. This class B G protein-coupled receptor binds peptides of the calcitonin gene-related peptide (CGRP) family, and its activation results in a marked increase in cytosolic cAMP and subsequent activation of protein kinase A, supposing a coupling to adenylyl cyclase (19,33). Notably, CRLR alone exhibits little affinity to its ligands and becomes ligand selective only when associated with one of the three...

show abstract

Effect of Factor XIII on Endothelial Barrier Function

Cited by 66 publications

References 32 publications

Insulin Stabilizes Microvascular Endothelial Barrier Function via Phosphatidylinositol 3-Kinase/Akt-Mediated Rac1 Activation

Insulin Stabilizes Microvascular Endothelial Barrier Function via Phosphatidylinositol 3-Kinase/Akt-Mediated Rac1 Activation

Roles of transglutaminases in cardiac and vascular diseases

Intermedin/adrenomedullin-2 is a hypoxia-induced endothelial peptide that stabilizes pulmonary microvascular permeability

Contact Info

Product

Resources

About