Download PDF
Thromb Haemost 2014; 112(05): 1051-1064
DOI: 10.1160/th14-03-0258
Animal Models
Schattauer GmbH

Glucagon-like peptide-1 receptor agonist activation ameliorates venous thrombosis-induced arteriovenous fistula failure in chronic kidneyd isease

Chiang-Ting Chien
3   Department of Life Science, National Taiwan Normal University, Taipei, Taiwan
,
Shih-Chen Fan
1   Department of Occupational Therapy, College of Medicine, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan
,
Shao-Chieh Lin
6   Department of Surgery, Division of Colorectal Surgery, National Cheng Kung University Hospital, Tainan, Taiwan
7   Institute of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
,
Chang-Chih Kuo
2   Department of Occupational Therapy, Kaoshiung Medical University, Kaohsiung, Taiwan
,
Chih-Hui Yang
4   Department of Biological Science & Technology, College of Medicine, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan
,
Tzu-Ying Yu
1   Department of Occupational Therapy, College of Medicine, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan
,
Shih-Pin Lee
3   Department of Life Science, National Taiwan Normal University, Taipei, Taiwan
,
Dai-Yu Cheng
5   Department of Bioengineering, College of Engineering, Ta-Tung University, Taipei, Taiwan
,
Ping-Chia Li
1   Department of Occupational Therapy, College of Medicine, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan
› Author Affiliations Financial support: This work was supported by grants from the National Science Council of the Republic of China (NSC98–2320-B002–043-MY3 and NSC98–2314-B-214–001-MY3), and ISU102–07–02.
Further Information

Publication History

Received: 25 March 2014

Accepted after minor revision: 08 May 2014

Publication Date:
20 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

High shear stress that develops in the arteriovenous fistula of chronic kidney diseases (CKD) may increase H2O2 and thromboxane A2 (TXA2) release, thereby exacerbating endothelial dysfunction, thrombosis, and neointimal hyperplasia. We investigated whether glucagon-like peptide-1 receptor agonist/exendin-4, a potentially cardiovascular protective agent, could improve TXA2-induced arteriovenous fistula injury in CKD. TXA2 administration to H2O2-exposed human umbilical vein endothelial cells increased apoptosis, senescence, and detachment; these phenotypes were associated with the downregulation of phosphorylated endothelial nitric oxide synthase/heme oxygenase-1 (eNOS/HO-1) signalling. Exendin-4 reduced H2O2/TXA2-induced endothelial injury via inhibition of apoptosis-related mechanisms and restoration of phosphorylated eNOS/HO-1 signalling. Male Wistar rats subjected to right common carotid artery-external jugular vein anastomosis were treated with exendin-4 via cervical implant osmotic pumps for 16–42 days. High shear stress induced by the arteriovenous fistula significantly increased venous haemodynamics, blood and tissue H2O2 and TXB2 levels, macrophage/monocyte infiltration, fibrosis, proliferation, and adhesion molecule-1 expression. Apoptosis was also increased due to NADPH oxidase gp91 activation and mitochondrial Bax translocation in the proximal end of the jugular vein of CKD rats. Exendin-4-treatment of rats with CKD led to the restoration of normal endothelial morphology and correction of arteriovenous fistula function. Exendin-4 treatment or thromboxane synthase gene deletion in CKD mice markedly reduced ADP-stimulated platelet adhesion to venous endothelium, and prevented venous occlusion in FeCl3-injured vessels by upregulation of HO-1. Together, these data reveal that the use of glucagon-like peptide-1 receptor agonists is an effective strategy for treatment of CKD-induced arteriovenous fistula failure.

Keywords

Apoptosis - free radicals - peripheral vascular disease - glucagon-like peptide-1 - thrombosis

 

  • References

  • 1 Anwar MA, Shalhoub J, Lim CS. et al. The effect of pressure-induced mechanical stretch on vascular wall differential gene expression.. J Vasc Res 2012; 49: 463-478.
    CrossrefPubMedGoogle Scholar
  • 2 Tsapenko MV, d’Uscio LV, Grande JP. et al. Increased production of superoxide anion contributes to dysfunction of the arteriovenous fistula.. Am J Physiol Renal Physiol 2012; 303: F1601-1607.
    CrossrefPubMedGoogle Scholar
  • 3 Croatt AJ, Grande JP, Hernandez MC. et al. Characterization of a model of an arteriovenous fistula in the rat: the effect of L-NAME.. Am J Pathol 2010; 176: 2530-2541.
    CrossrefPubMedGoogle Scholar
  • 4 Oeseburg H, de Boer RA, Buikema H. et al. Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A.. Arterioscler Thromb Vasc Biol 2010; 30: 1407-1414.
    CrossrefPubMedGoogle Scholar
  • 5 Hoffmann J, Haendeler J, Aicher A. et al. Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide.. Circ Res 2001; 89: 709-715.
    CrossrefPubMedGoogle Scholar
  • 6 Uraoka M, Ikeda K, Kurimoto-Nakano R. et al. Loss of bcl-2 during the senescence exacerbates the impaired angiogenic functions in endothelial cells by deteriorating the mitochondrial redox state.. Hypertension 2011; 58: 254-263.
    CrossrefPubMedGoogle Scholar
  • 7 Karamouzis I, Grekas D, Karamouzis M. et al. Physical training in patients on hemodialysis has a beneficial effect on the levels of eicosanoid hormone-like substances.. Hormones 2009; 8: 129-137.
    CrossrefPubMedGoogle Scholar
  • 8 Smyth EM. Thromboxane and the thromboxane receptor in cardiovascular disease.. Clin Lipidol 2010; 5: 209-219.
    CrossrefPubMedGoogle Scholar
  • 9 Zhang M, Song P, Xu J. et al. Activation of NAD(P)H oxidases by thromboxane A2 receptor uncouples endothelial nitric oxide synthase.. Arterioscler Thromb Vasc Biol 2011; 31: 125-132.
    CrossrefPubMedGoogle Scholar
  • 10 Siangjong L, Gauthier KM, Pfister SL. et al. Endothelial 12(S)-HETE vasorelaxation is mediated by thromboxane receptor inhibition in mouse mesenteric arteries.. Am J Physiol Heart Circ Physiol 2013; 304: H382-392.
    CrossrefPubMedGoogle Scholar
  • 11 Yoo HV, Oark SJ, Seo EY. et al. Role of thromboxane A2-activated nonselective cation channels in hypoxic pulmonary vasoconstriction of rat.. Am J Physiol Cell Physiol 2012; 302: C307-317.
    CrossrefPubMedGoogle Scholar
  • 12 Dember LM, Beck GJ, Allon M. et al. Dialysis Access Consortium Study Group. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial.. J Am Med Assoc 2008; 299: 2164-2171.
    CrossrefPubMedGoogle Scholar
  • 13 Roan JN, Fang SY, Chang SW. et al. Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model.. J Vasc Surg 2012; 56: 1381-1389.
    CrossrefPubMedGoogle Scholar
  • 14 Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands.. Br J Pharmacol 2012; 166: 27-41.
    CrossrefPubMedGoogle Scholar
  • 15 Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas.. Pharmacol Ther 2007; 113: 546-593.
    CrossrefPubMedGoogle Scholar
  • 16 Kielgast U, Holst JJ, Madsbad S. Treatment of type 1 diabetic patients with glucagon-like peptide-1 (GLP-1) and GLP-1R agonists.. Curr Diabetes Rev 2009; 5: 266-275.
    CrossrefPubMedGoogle Scholar
  • 17 Noyan-Ashraf MH, Momen MA, Ban K. et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice.. Diabetes 2009; 58: 975-983.
    CrossrefPubMedGoogle Scholar
  • 18 Nystrom T, Gutniak MK, Zhang Q. et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease.. Am J Physiol Endocrinol Metab 2004; 287: E1209-1215.
    CrossrefPubMedGoogle Scholar
  • 19 Xie Y, Wang SX, Sha WW. et al. Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation.. Chin Med J 2008; 121: 2134-2138.
    PubMedGoogle Scholar
  • 20 Shiraki A, Oyama JI, Komoda H. et al. The glucagon-like peptide 1 analog liraglutide reduces TNF-alpha-induced oxidative stress and inflammation in endothelial cells.. Atherosclerosis 2012; 221: 375-382.
    CrossrefPubMedGoogle Scholar
  • 21 Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP.. Gastroenterology 2007; 132: 2131-2157.
    CrossrefPubMedGoogle Scholar
  • 22 Thum A, Hupe-Sodmann K, Goke R. et al. Endoproteolysis by isolated membrane peptidases reveal metabolic stability of glucagon-like peptide-1 analogs, exendins-3 and -4.. Exp Clin Endocrinol Diabetes 2001; 110: 113-118.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Chen J, Couto FM, Minn AH. et al. Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-interacting protein.. Biochem Biophys Res Commun 2006; 346: 1067-1074.
    CrossrefPubMedGoogle Scholar
  • 24 Li Y, Hansotia T, Yusta B. et al. Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis.. J Biol Chem 2003; 278: 471-478.
    CrossrefPubMedGoogle Scholar
  • 25 Ferdaoussi M, Abdelli S, Yang JY. et al. Exendin-4 protects beta-cells from inter-leukin-1 beta-induced apoptosis by interfering with the c-jun nh2-terminal kinase pathway.. Diabetes 2008; 57: 1205-1215.
    CrossrefPubMedGoogle Scholar
  • 26 Choi SE, Min SH, Shin HC. et al. Involvement of calcium-mediated apoptotic signals in H2O2-induced MIN6N8a cell death.. Eur J Pharmacol 2006; 547: 1-9.
    CrossrefPubMedGoogle Scholar
  • 27 Lei X, Reheman A, Hou Y. et al. Anfibatide, a novel GPIb complex antagonist, inhibits platelet adhesion and thrombus formation in vitro and in vivo in murine models of thrombosis.. Thromb Haemost 2014; 111: 279-289.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Berdeaux O, Chardigny JM, Sébédio JL. et al. Effects of a trans isomer of arachidonic acid on rat platelet aggregation and eicosanoid production.. J Lipid Res 1996; 37: 2244-2250.
    PubMedGoogle Scholar
  • 29 Akishita M, Nagai K, Xi H. et al. Renin-angiotensin system modulates oxidative stress-induced endothelial cell apoptosis in rats.. Hypertension 2005; 45: 1188-1193.
    CrossrefPubMedGoogle Scholar
  • 30 Noyan-Ashraf MH, Shikatani EA, Schuiki I. et al. A glucagon-like peptide-1 analog reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity.. Circulation 2013; 127: 74-85.
    CrossrefPubMedGoogle Scholar
  • 31 Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall.. Circ Res 2001; 88: 877-887.
    CrossrefPubMedGoogle Scholar
  • 32 Ban K, Noyan-Ashraf MH, Hoefer J. et al. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and-independent pathways.. Circulation 2008; 117: 2340-2350.
    CrossrefPubMedGoogle Scholar
  • 33 Green BD, Hand KV, Dougan JE. et al. GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP.. Arch Biochem Biophys 2008; 478: 136-142.
    CrossrefPubMedGoogle Scholar
  • 34 Cabou C, Campistron G, Marsollier N. et al. Brain glucagon-like peptide-1 regulates arterial blood flow, heart rate, and insulin sensitivity.. Diabetes 2008; 57: 2577-2587.
    CrossrefPubMedGoogle Scholar
  • 35 Shan HY, Bai XJ, Chen XM. Apoptosis is involved in the senescence of endothelial cells induced by angiotensin II.. Cell Biol Int 2008; 32: 264-270.
    CrossrefPubMedGoogle Scholar
  • 36 Naranmandura H, Chen X, Tanaka M. et al. Release of apoptotic cytochrome C from mitochondria by dimethylarsinous acid occurs through interaction with voltage-dependent anion channel in vitro.. Toxicol Sci 2012; 128: 137-146.
    CrossrefPubMedGoogle Scholar
  • 37 Arbel N, Shoshan-Barmatz V. Voltage-dependent anion channel 1-based peptides interact with Bcl-2 to prevent antiapoptotic activity.. J Biol Chem 2010; 285: 6053-6062.
    CrossrefPubMedGoogle Scholar
  • 38 Chien CT, Chang TC, Tsai CY. et al. Adenovirus-mediated bcl-2 gene transfer inhibits renal ischemia/reperfusion induced tubular oxidative stress and apoptosis.. Am J Transplant 2005; 5: 1194-1203.
    CrossrefPubMedGoogle Scholar
  • 39 Flores-Delgado G, Liu CWY, Sposto R. et al. A limited screen for protein interactions reveals new roles for protein phosphatase 1 in cell cycle control and apoptosis.. J Proteome Res 2007; 6: 1165-1175.
    CrossrefPubMedGoogle Scholar
  • 40 Martin D, Salinas M, Fujita N. et al. Ceramide and reactive oxygen species generated by H2O2 induce caspase-3-independent degradation of Akt/protein kinase B.. J Biol Chem 2002; 277: 42943-42952.
    CrossrefPubMedGoogle Scholar
  • 41 Li PC, Yang CC, Hsu SP. et al. Repetitive progressive thermal preconditioning hinders thrombosis by reinforcing phosphatidylinositol 3-kinase/Akt-dependent heat-shock protein/endothelial nitric oxide synthase signaling.. J Vasc Surg 2012; 56: 159-170.
    CrossrefPubMedGoogle Scholar
  • 42 Salinas M, Wang J, de Sagarra MR. et al. Protein kinase Akt/PKB phosphorylates heme oxygenase-1 in vitro and in vivo.. FEBS Lett 2004; 578: 90-94.
    CrossrefPubMedGoogle Scholar
  • 43 Deng X, Gao F, May WS Jr. Bcl2 retards G1/S cell cycle transition by regulating intracellular ROS.. Blood 2003; 102: 3179-3185.
    CrossrefPubMedGoogle Scholar
  • 44 Erdogdu O, Nathanson D, Sjoholm A. et al. Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor.. Mol Cell Endocrinol 2010; 325: 26-35.
    CrossrefPubMedGoogle Scholar
  • 45 Kimura R, Okouchi M, Fujioka H. et al. Glucagon-like peptide-1 (GLP-1) protects against methylglyoxal-induced pc12 cell apoptosis through the PI3K/Akt/ mTor/GCLC/redox signaling pathway.. Neuroscience 2009; 162: 1212-1219.
    CrossrefPubMedGoogle Scholar
  • 46 Rücker M, Laschke MW, Stamm A. et al. Local preconditioning by thermal stress accelerates microvascular thrombus formation.. Shock 2009; 31: 627-633.
    CrossrefPubMedGoogle Scholar
  • 47 Falk E. Thrombosis in unstable angina: pathologic aspects. In: Thrombosis and Platelets in Myocardial Ischemia.. Philadelphia: F.A. Davis Publishers; 1987. pp. 137-149.
    Google Scholar
  • 48 Lindenblatt N, Schareck W, Belusa L. et al. Anti-oxidant ebselen delays micro-vascular thrombus formation in the rat cremaster muscle by inhibiting platelet P-selectin expression.. Thromb Haemost 2003; 90: 882-892.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Luo Z, Fujio Y, Kureishi Y. et al. Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo.. J Clin Invest 2000; 106: 493-499.
    CrossrefPubMedGoogle Scholar
  • 50 Maier JA, Bernardini D, Rayssiguier Y. et al. High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro.. Biochim Biophys Acta 2004; 1689: 6-12.
    CrossrefPubMedGoogle Scholar