Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways

Authors: Lili Shi, Ye Ji, Xiaoyan Jiang, Lihong Zhou, Ying Xu, Yanbo Li, Wei Jiang, Ping Meng, Xiaomin Liu

Published in: Cardiovascular Diabetology | Issue 1/2015

Login to get access

Abstract

Background

As a new anti-diabetic medicine, Liraglutide (LIRA), one of GLP-1 analogues, has been found to have an anti-atherosclerotic effect. Since vascular smooth muscle cells (VSMCs) play pivotal roles in the occurrence of diabetic atherosclerosis, it is important to investigate the role of LIRA in reducing the harmful effects of high-glucose (HG) treatment in cultured VSMCs, and identifying associated molecular mechanisms.

Methods

Primary rat VSMCs were exposed to low or high glucose-containing medium with or without LIRA. They were challenged with HG in the presence of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2, or glucagon-like peptide receptor (GLP-1R) inhibitors. Cell proliferation and viability was evaluated using a Cell Counting Kit-8. Cell migration was determined by Transwell migration and scratch wound assays. Flow cytometry and Western blotting were used to determine apoptosis and protein expression, respectively.

Results

Under the HG treatment, VSMCs exhibited increased migration, proliferation, and phosphorylation of protein kinase B (Akt) and ERK1/2, along with reduced apoptosis (all p < 0.01 vs. control). These effects were significantly attenuated with LIRA co-treatment (all p < 0.05 vs. HG alone). Inhibition of PI3K kinase and ERK1/2 similarly attenuated the HG-induced effects (all p < 0.01 vs. HG alone). GLP-1R inhibitors effectively reversed the beneficial effects of LIRA on HG treatment (all p < 0.05).

Conclusions

HG treatment may induce abnormal phenotypes in VSMCs via PI3K and ERK1/2 signaling pathways activated by GLP-1R, and LIRA may protect cells from HG damage by acting on these same pathways.
Literature
1.
2.
go back to reference Angeli FS, Shannon RP. Beyond glycemic control: cardiovascular effects of incretin-based therapies. Front Horm Res. 2014;43:144–57.PubMed Angeli FS, Shannon RP. Beyond glycemic control: cardiovascular effects of incretin-based therapies. Front Horm Res. 2014;43:144–57.PubMed
3.
go back to reference Doran AC, Meller N, McNamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol. 2008;28:812–9.CrossRefPubMedCentralPubMed Doran AC, Meller N, McNamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol. 2008;28:812–9.CrossRefPubMedCentralPubMed
5.
go back to reference Newby AC, Zaltsman AB. Fibrous cap formation or destruction–the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation. Cardiovasc Res. 1999;41:345–60.CrossRefPubMed Newby AC, Zaltsman AB. Fibrous cap formation or destruction–the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation. Cardiovasc Res. 1999;41:345–60.CrossRefPubMed
6.
go back to reference Walsh K, Smith RC, Kim HS. Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000;87:184–8.CrossRefPubMed Walsh K, Smith RC, Kim HS. Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res. 2000;87:184–8.CrossRefPubMed
7.
go back to reference Ruiz E, Gordillo-Moscoso A, Padilla E, Redondo S, Rodriguez E, Reguillo F, et al. Human vascular smooth muscle cells from diabetic patients are resistant to induced apoptosis due to high Bcl-2 expression. Diabetes. 2006;55:1243–51.CrossRefPubMed Ruiz E, Gordillo-Moscoso A, Padilla E, Redondo S, Rodriguez E, Reguillo F, et al. Human vascular smooth muscle cells from diabetic patients are resistant to induced apoptosis due to high Bcl-2 expression. Diabetes. 2006;55:1243–51.CrossRefPubMed
8.
go back to reference Ruiz E, Redondo S, Gordillo-Moscoso A, Tejerina T. Pioglitazone induces apoptosis in human vascular smooth muscle cells from diabetic patients involving the transforming growth factor-beta/activin receptor-like kinase-4/5/7/Smad2 signaling pathway. J Pharmacol Exp Ther. 2007;321:431–8.CrossRefPubMed Ruiz E, Redondo S, Gordillo-Moscoso A, Tejerina T. Pioglitazone induces apoptosis in human vascular smooth muscle cells from diabetic patients involving the transforming growth factor-beta/activin receptor-like kinase-4/5/7/Smad2 signaling pathway. J Pharmacol Exp Ther. 2007;321:431–8.CrossRefPubMed
10.
go back to reference Song BJ, Soh Y, Bae M, Pie J, Wan J, Jeong K. Apoptosis of PC12 cells by 4-hydroxy-2-nonenal is mediated through selective activation of the c-Jun N-terminal protein kinase pathway. Chem Biol Interact. 2001;130–132:943–54.CrossRefPubMed Song BJ, Soh Y, Bae M, Pie J, Wan J, Jeong K. Apoptosis of PC12 cells by 4-hydroxy-2-nonenal is mediated through selective activation of the c-Jun N-terminal protein kinase pathway. Chem Biol Interact. 2001;130–132:943–54.CrossRefPubMed
11.
go back to reference Whiteman EL, Cho H, Birnbaum MJ. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab. 2002;13:444–51.CrossRefPubMed Whiteman EL, Cho H, Birnbaum MJ. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab. 2002;13:444–51.CrossRefPubMed
13.
go back to reference Natarajan R, Scott S, Bai W, Yerneni KK, Nadler J. Angiotensin II signaling in vascular smooth muscle cells under high glucose conditions. Hypertension. 1999;33:378–84.CrossRefPubMed Natarajan R, Scott S, Bai W, Yerneni KK, Nadler J. Angiotensin II signaling in vascular smooth muscle cells under high glucose conditions. Hypertension. 1999;33:378–84.CrossRefPubMed
14.
go back to reference Igarashi M, Wakasaki H, Takahara N, Ishii H, Jiang ZY, Yamauchi T, et al. Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J Clin Invest. 1999;103:185–95.CrossRefPubMedCentralPubMed Igarashi M, Wakasaki H, Takahara N, Ishii H, Jiang ZY, Yamauchi T, et al. Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J Clin Invest. 1999;103:185–95.CrossRefPubMedCentralPubMed
15.
go back to reference Campbell M, Trimble ER. Modification of PI3K- and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CbetaII. Circ Res. 2005;96:197–206.CrossRefPubMed Campbell M, Trimble ER. Modification of PI3K- and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CbetaII. Circ Res. 2005;96:197–206.CrossRefPubMed
16.
go back to reference Sakuma H, Yamamoto M, Okumura M, Kojima T, Maruyama T, Yasuda K. High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1. Am J Physiol Cell Physiol. 2002;283:C422–428.CrossRefPubMed Sakuma H, Yamamoto M, Okumura M, Kojima T, Maruyama T, Yasuda K. High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1. Am J Physiol Cell Physiol. 2002;283:C422–428.CrossRefPubMed
17.
go back to reference Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J. Mechanisms of action of troglitazone in the prevention of high glucose-induced migration and proliferation of cultured coronary smooth muscle cells. Circ Res. 1997;81:953–62.CrossRefPubMed Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J. Mechanisms of action of troglitazone in the prevention of high glucose-induced migration and proliferation of cultured coronary smooth muscle cells. Circ Res. 1997;81:953–62.CrossRefPubMed
18.
go back to reference Allen TR, Krueger KD, Hunter 3rd WJ, Agrawal DK. Evidence that insulin-like growth factor-1 requires protein kinase C-epsilon, PI3-kinase and mitogen-activated protein kinase pathways to protect human vascular smooth muscle cells from apoptosis. Immunol Cell Biol. 2005;83:651–67.CrossRefPubMed Allen TR, Krueger KD, Hunter 3rd WJ, Agrawal DK. Evidence that insulin-like growth factor-1 requires protein kinase C-epsilon, PI3-kinase and mitogen-activated protein kinase pathways to protect human vascular smooth muscle cells from apoptosis. Immunol Cell Biol. 2005;83:651–67.CrossRefPubMed
19.
go back to reference Wang W, Prince CZ, Mou Y, Pollman MJ. Notch3 signaling in vascular smooth muscle cells induces c-FLIP expression via ERK/MAPK activation. Resistance to Fas ligand-induced apoptosis. J Biol Chem. 2002;277:21723–9.CrossRefPubMed Wang W, Prince CZ, Mou Y, Pollman MJ. Notch3 signaling in vascular smooth muscle cells induces c-FLIP expression via ERK/MAPK activation. Resistance to Fas ligand-induced apoptosis. J Biol Chem. 2002;277:21723–9.CrossRefPubMed
20.
go back to reference Cui RR, Mao DA, Yi L, Wang C, Zhang XX, Xie H, et al. Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways. Amino Acids. 2010;39:1193–200.CrossRefPubMed Cui RR, Mao DA, Yi L, Wang C, Zhang XX, Xie H, et al. Apelin suppresses apoptosis of human vascular smooth muscle cells via APJ/PI3-K/Akt signaling pathways. Amino Acids. 2010;39:1193–200.CrossRefPubMed
21.
go back to reference Allen RT, Krueger KD, Dhume A, Agrawal DK. Sustained Akt/PKB activation and transient attenuation of c-jun N-terminal kinase in the inhibition of apoptosis by IGF-1 in vascular smooth muscle cells. Apoptosis. 2005;10:525–35.CrossRefPubMed Allen RT, Krueger KD, Dhume A, Agrawal DK. Sustained Akt/PKB activation and transient attenuation of c-jun N-terminal kinase in the inhibition of apoptosis by IGF-1 in vascular smooth muscle cells. Apoptosis. 2005;10:525–35.CrossRefPubMed
22.
go back to reference Li H, Peng W, Zhuang J, Lu Y, Jian W, Wei Y, et al. Vaspin attenuates high glucose-induced vascular smooth muscle cells proliferation and chemokinesis by inhibiting the MAPK, PI3K/Akt, and NF-kappaB signaling pathways. Atherosclerosis. 2013;228:61–8.CrossRefPubMed Li H, Peng W, Zhuang J, Lu Y, Jian W, Wei Y, et al. Vaspin attenuates high glucose-induced vascular smooth muscle cells proliferation and chemokinesis by inhibiting the MAPK, PI3K/Akt, and NF-kappaB signaling pathways. Atherosclerosis. 2013;228:61–8.CrossRefPubMed
23.
go back to reference Igarashi M, Hirata A, Yamaguchi H, Sugae N, Kadomoto-Antsuki Y, Nozaki H, et al. Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats. J Atheroscler Thromb. 2007;14:235–44.CrossRefPubMed Igarashi M, Hirata A, Yamaguchi H, Sugae N, Kadomoto-Antsuki Y, Nozaki H, et al. Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats. J Atheroscler Thromb. 2007;14:235–44.CrossRefPubMed
25.
go back to reference Mafong DD, Henry RR. Exenatide as a treatment for diabetes and obesity: implications for cardiovascular risk reduction. Curr Atheroscler Rep. 2008;10:55–60.CrossRefPubMed Mafong DD, Henry RR. Exenatide as a treatment for diabetes and obesity: implications for cardiovascular risk reduction. Curr Atheroscler Rep. 2008;10:55–60.CrossRefPubMed
26.
go back to reference Bunck MC, Diamant M, Eliasson B, Corner A, Shaginian RM, Heine RJ, et al. Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care. 2010;33:1734–7.CrossRefPubMedCentralPubMed Bunck MC, Diamant M, Eliasson B, Corner A, Shaginian RM, Heine RJ, et al. Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care. 2010;33:1734–7.CrossRefPubMedCentralPubMed
27.
go back to reference Horton ES, Silberman C, Davis KL, Berria R. Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010;33:1759–65.CrossRefPubMedCentralPubMed Horton ES, Silberman C, Davis KL, Berria R. Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010;33:1759–65.CrossRefPubMedCentralPubMed
28.
go back to reference Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24:275–86.PubMed Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008;24:275–86.PubMed
29.
30.
go back to reference Rose BA, Force T, Wang Y. Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev. 2010;90:1507–46.CrossRefPubMed Rose BA, Force T, Wang Y. Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev. 2010;90:1507–46.CrossRefPubMed
31.
go back to reference Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009;58:975–83.CrossRefPubMedCentralPubMed Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009;58:975–83.CrossRefPubMedCentralPubMed
32.
go back to reference Gaspari T, Liu H, Welungoda I, Hu Y, Widdop RE, Knudsen LB, et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE−/− mouse model. Diab Vasc Dis Res. 2011;8:117–24.CrossRefPubMed Gaspari T, Liu H, Welungoda I, Hu Y, Widdop RE, Knudsen LB, et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE−/− mouse model. Diab Vasc Dis Res. 2011;8:117–24.CrossRefPubMed
33.
go back to reference Ceriello A, Esposito K, Testa R, Bonfigli AR, Marra M, Giugliano D. The possible protective role of glucagon-like peptide 1 on endothelium during the meal and evidence for an “endothelial resistance” to glucagon-like peptide 1 in diabetes. Diabetes Care. 2011;34:697–702.CrossRefPubMedCentralPubMed Ceriello A, Esposito K, Testa R, Bonfigli AR, Marra M, Giugliano D. The possible protective role of glucagon-like peptide 1 on endothelium during the meal and evidence for an “endothelial resistance” to glucagon-like peptide 1 in diabetes. Diabetes Care. 2011;34:697–702.CrossRefPubMedCentralPubMed
34.
go back to reference Nagashima M, Watanabe T, Terasaki M, Tomoyasu M, Nohtomi K, Kim-Kaneyama J, et al. Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice. Diabetologia. 2011;54:2649–59.CrossRefPubMedCentralPubMed Nagashima M, Watanabe T, Terasaki M, Tomoyasu M, Nohtomi K, Kim-Kaneyama J, et al. Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice. Diabetologia. 2011;54:2649–59.CrossRefPubMedCentralPubMed
35.
go back to reference Aronoff DM, Canetti C, Serezani CH, Luo M, Peters-Golden M. Cutting edge: macrophage inhibition by cyclic AMP (cAMP): differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol. 2005;174:595–9.CrossRefPubMed Aronoff DM, Canetti C, Serezani CH, Luo M, Peters-Golden M. Cutting edge: macrophage inhibition by cyclic AMP (cAMP): differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol. 2005;174:595–9.CrossRefPubMed
36.
go back to reference Mogi C, Tobo M, Tomura H, Murata N, He XD, Sato K, et al. Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages. J Immunol. 2009;182:3243–51.CrossRefPubMed Mogi C, Tobo M, Tomura H, Murata N, He XD, Sato K, et al. Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages. J Immunol. 2009;182:3243–51.CrossRefPubMed
37.
go back to reference Goto H, Nomiyama T, Mita T, Yasunari E, Azuma K, Komiya K, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury. Biochem Biophys Res Commun. 2011;405:79–84.CrossRefPubMed Goto H, Nomiyama T, Mita T, Yasunari E, Azuma K, Komiya K, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury. Biochem Biophys Res Commun. 2011;405:79–84.CrossRefPubMed
38.
go back to reference Arakawa M, Mita T, Azuma K, Ebato C, Goto H, Nomiyama T, et al. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes. 2010;59:1030–7.CrossRefPubMedCentralPubMed Arakawa M, Mita T, Azuma K, Ebato C, Goto H, Nomiyama T, et al. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes. 2010;59:1030–7.CrossRefPubMedCentralPubMed
40.
go back to reference Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, 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.CrossRefPubMed Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, 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.CrossRefPubMed
41.
go back to reference Ban K, Kim KH, Cho CK, Sauve M, Diamandis EP, Backx PH, et al. Glucagon-like peptide (GLP)-1(9–36)amide-mediated cytoprotection is blocked by exendin(9–39) yet does not require the known GLP-1 receptor. Endocrinology. 2010;151:1520–31.CrossRefPubMed Ban K, Kim KH, Cho CK, Sauve M, Diamandis EP, Backx PH, et al. Glucagon-like peptide (GLP)-1(9–36)amide-mediated cytoprotection is blocked by exendin(9–39) yet does not require the known GLP-1 receptor. Endocrinology. 2010;151:1520–31.CrossRefPubMed
42.
go back to reference Wang SX, Xie Y, Zhou X, Sha WW, Wang WL, Han LP, et al. Effect of glucagon-like peptide-1 on hypoxia-reoxygenation induced injury in neonatal rat cardiomyocytes. Zhonghua Xin Xue Guan Bing Za Zhi. 2010;38:72–5.PubMed Wang SX, Xie Y, Zhou X, Sha WW, Wang WL, Han LP, et al. Effect of glucagon-like peptide-1 on hypoxia-reoxygenation induced injury in neonatal rat cardiomyocytes. Zhonghua Xin Xue Guan Bing Za Zhi. 2010;38:72–5.PubMed
43.
go back to reference Ravassa S, Zudaire A, Carr RD, Diez J. Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am J Physiol Heart Circ Physiol. 2011;300:H1361–1372.CrossRefPubMed Ravassa S, Zudaire A, Carr RD, Diez J. Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am J Physiol Heart Circ Physiol. 2011;300:H1361–1372.CrossRefPubMed
44.
go back to reference Erdogdu O, Nathanson D, Sjoholm A, Nystrom T, Zhang Q. 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.CrossRefPubMed Erdogdu O, Nathanson D, Sjoholm A, Nystrom T, Zhang Q. 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.CrossRefPubMed
45.
go back to reference Fehmann HC, Jiang J, Schweinfurth J, Dorsch K, Wheeler MB, Boyd 3rd AE, et al. Ligand-specificity of the rat GLP-I receptor recombinantly expressed in Chinese hamster ovary (CHO-) cells. Z Gastroenterol. 1994;32:203–7.PubMed Fehmann HC, Jiang J, Schweinfurth J, Dorsch K, Wheeler MB, Boyd 3rd AE, et al. Ligand-specificity of the rat GLP-I receptor recombinantly expressed in Chinese hamster ovary (CHO-) cells. Z Gastroenterol. 1994;32:203–7.PubMed
46.
go back to reference Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A. 1987;84:3434–8.CrossRefPubMedCentralPubMed Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A. 1987;84:3434–8.CrossRefPubMedCentralPubMed
47.
go back to reference Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. 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;117:2340–50.CrossRefPubMed Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. 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;117:2340–50.CrossRefPubMed
48.
go back to reference Hirata Y, Kurobe H, Nishio C, Tanaka K, Fukuda D, Uematsu E, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury. Eur J Pharmacol. 2013;699:106–11.CrossRefPubMed Hirata Y, Kurobe H, Nishio C, Tanaka K, Fukuda D, Uematsu E, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury. Eur J Pharmacol. 2013;699:106–11.CrossRefPubMed
49.
go back to reference Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage. 2012;20:256–60.CrossRefPubMed Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage. 2012;20:256–60.CrossRefPubMed
50.
go back to reference Chamley-Campbell J, Campbell GR, Ross R. The smooth muscle cell in culture. Physiol Rev. 1979;59:1–61.PubMed Chamley-Campbell J, Campbell GR, Ross R. The smooth muscle cell in culture. Physiol Rev. 1979;59:1–61.PubMed
51.
go back to reference Noyan-Ashraf MH, Shikatani EA, Schuiki I, Mukovozov I, Wu J, Li RK, 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.CrossRefPubMed Noyan-Ashraf MH, Shikatani EA, Schuiki I, Mukovozov I, Wu J, Li RK, 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.CrossRefPubMed
52.
go back to reference Zhang J, Fu M, Zhu X, Xiao Y, Mou Y, Zheng H, et al. Peroxisome proliferator-activated receptor delta is up-regulated during vascular lesion formation and promotes post-confluent cell proliferation in vascular smooth muscle cells. J Biol Chem. 2002;277:11505–12.CrossRefPubMed Zhang J, Fu M, Zhu X, Xiao Y, Mou Y, Zheng H, et al. Peroxisome proliferator-activated receptor delta is up-regulated during vascular lesion formation and promotes post-confluent cell proliferation in vascular smooth muscle cells. J Biol Chem. 2002;277:11505–12.CrossRefPubMed
53.
go back to reference Qin L, Yang YB, Yang YX, Zhu N, Gong YZ, Zhang CP, et al. Ezetimibe suppresses cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling. Acta Pharmacol Sin. 2014;35:1129–36.CrossRefPubMedCentralPubMed Qin L, Yang YB, Yang YX, Zhu N, Gong YZ, Zhang CP, et al. Ezetimibe suppresses cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling. Acta Pharmacol Sin. 2014;35:1129–36.CrossRefPubMedCentralPubMed
54.
go back to reference Guo LX, Xia ZN, Gao X, Yin F, Liu JH. Glucagon-like peptide 1 receptor plays a critical role in geniposide-regulated insulin secretion in INS-1 cells. Acta Pharmacol Sin. 2012;33:237–41.CrossRefPubMedCentralPubMed Guo LX, Xia ZN, Gao X, Yin F, Liu JH. Glucagon-like peptide 1 receptor plays a critical role in geniposide-regulated insulin secretion in INS-1 cells. Acta Pharmacol Sin. 2012;33:237–41.CrossRefPubMedCentralPubMed
55.
go back to reference Younce CW, Burmeister MA, Ayala JE. Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Am J Physiol Cell Physiol. 2013;304:C508–518.CrossRefPubMed Younce CW, Burmeister MA, Ayala JE. Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Am J Physiol Cell Physiol. 2013;304:C508–518.CrossRefPubMed
56.
go back to reference Liu J, Ren Y, Kang L, Zhang L. Oxidized low-density lipoprotein increases the proliferation and migration of human coronary artery smooth muscle cells through the upregulation of osteopontin. Int J Mol Med. 2014;33:1341–7.PubMed Liu J, Ren Y, Kang L, Zhang L. Oxidized low-density lipoprotein increases the proliferation and migration of human coronary artery smooth muscle cells through the upregulation of osteopontin. Int J Mol Med. 2014;33:1341–7.PubMed
57.
go back to reference Vartak-Sharma N, Ghorpade A. Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration. J Neuroinflammation. 2012;9:195.CrossRefPubMedCentralPubMed Vartak-Sharma N, Ghorpade A. Astrocyte elevated gene-1 regulates astrocyte responses to neural injury: implications for reactive astrogliosis and neurodegeneration. J Neuroinflammation. 2012;9:195.CrossRefPubMedCentralPubMed
58.
go back to reference Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.CrossRefPubMed Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.CrossRefPubMed
59.
go back to reference Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.CrossRefPubMed Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.CrossRefPubMed
60.
go back to reference Killilea T. Long-term consequences of type 2 diabetes mellitus: economic impact on society and managed care. Am J Manag Care. 2002;8:S441–449.PubMed Killilea T. Long-term consequences of type 2 diabetes mellitus: economic impact on society and managed care. Am J Manag Care. 2002;8:S441–449.PubMed
61.
62.
go back to reference Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose. Circulation. 1999;99:1370–8.CrossRefPubMed Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose. Circulation. 1999;99:1370–8.CrossRefPubMed
63.
go back to reference Hall JL, Matter CM, Wang X, Gibbons GH. Hyperglycemia inhibits vascular smooth muscle cell apoptosis through a protein kinase C-dependent pathway. Circ Res. 2000;87:574–80.CrossRefPubMed Hall JL, Matter CM, Wang X, Gibbons GH. Hyperglycemia inhibits vascular smooth muscle cell apoptosis through a protein kinase C-dependent pathway. Circ Res. 2000;87:574–80.CrossRefPubMed
64.
go back to reference You B, Ren A, Yan G, Sun J. Activation of sphingosine kinase-1 mediates inhibition of vascular smooth muscle cell apoptosis by hyperglycemia. Diabetes. 2007;56:1445–53.CrossRefPubMed You B, Ren A, Yan G, Sun J. Activation of sphingosine kinase-1 mediates inhibition of vascular smooth muscle cell apoptosis by hyperglycemia. Diabetes. 2007;56:1445–53.CrossRefPubMed
65.
go back to reference Qin L, Yang YB, Yang YX, Gong YZ, Li XL, Li GY, et al. Inhibition of smooth muscle cell proliferation by ezetimibe via the cyclin D1-MAPK pathway. J Pharmacol Sci. 2014;125:283–91.CrossRefPubMed Qin L, Yang YB, Yang YX, Gong YZ, Li XL, Li GY, et al. Inhibition of smooth muscle cell proliferation by ezetimibe via the cyclin D1-MAPK pathway. J Pharmacol Sci. 2014;125:283–91.CrossRefPubMed
66.
go back to reference Isenovic ER, Kedees MH, Haidara MA, Trpkovic A, Mikhailidis DP, Marche P. Involvement of ERK1/2 kinase in insulin-and thrombin-stimulated vascular smooth muscle cell proliferation. Angiology. 2010;61:357–64.CrossRefPubMed Isenovic ER, Kedees MH, Haidara MA, Trpkovic A, Mikhailidis DP, Marche P. Involvement of ERK1/2 kinase in insulin-and thrombin-stimulated vascular smooth muscle cell proliferation. Angiology. 2010;61:357–64.CrossRefPubMed
67.
go back to reference Isenovic ER, Soskic S, Trpkovic A, Dobutovic B, Popovic M, Gluvic Z, et al. Insulin, thrombine, ERK1/2 kinase and vascular smooth muscle cells proliferation. Curr Pharm Des. 2010;16:3895–902.CrossRefPubMed Isenovic ER, Soskic S, Trpkovic A, Dobutovic B, Popovic M, Gluvic Z, et al. Insulin, thrombine, ERK1/2 kinase and vascular smooth muscle cells proliferation. Curr Pharm Des. 2010;16:3895–902.CrossRefPubMed
68.
go back to reference Koehler JA, Baggio LL, Cao X, Abdulla T, Campbell JE, Secher T, et al. Glucagon-like peptide-1 receptor agonists increase pancreatic mass by induction of protein synthesis. Diabetes. 2014. [epub ahead of print] Koehler JA, Baggio LL, Cao X, Abdulla T, Campbell JE, Secher T, et al. Glucagon-like peptide-1 receptor agonists increase pancreatic mass by induction of protein synthesis. Diabetes. 2014. [epub ahead of print]
69.
go back to reference Li CJ, Yu Q, Yu P, Yu TL, Zhang QM, Lu S, et al. Changes in liraglutide-induced body composition are related to modifications in plasma cardiac natriuretic peptides levels in obese type 2 diabetic patients. Cardiovasc Diabetol. 2014;13:36.CrossRefPubMedCentralPubMed Li CJ, Yu Q, Yu P, Yu TL, Zhang QM, Lu S, et al. Changes in liraglutide-induced body composition are related to modifications in plasma cardiac natriuretic peptides levels in obese type 2 diabetic patients. Cardiovasc Diabetol. 2014;13:36.CrossRefPubMedCentralPubMed
70.
go back to reference Bao W, Holt LJ, Prince RD, Jones GX, Aravindhan K, Szapacs M, et al. Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection against myocardial ischemia/reperfusion injury in the rat. Cardiovasc Diabetol. 2013;12:148.CrossRefPubMedCentralPubMed Bao W, Holt LJ, Prince RD, Jones GX, Aravindhan K, Szapacs M, et al. Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection against myocardial ischemia/reperfusion injury in the rat. Cardiovasc Diabetol. 2013;12:148.CrossRefPubMedCentralPubMed
71.
go back to reference Selley E, Kun S, Szijarto IA, Laczy B, Kovacs T, Fulop F, et al. Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production. Cardiovasc Diabetol. 2014;13:69.CrossRefPubMedCentralPubMed Selley E, Kun S, Szijarto IA, Laczy B, Kovacs T, Fulop F, et al. Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production. Cardiovasc Diabetol. 2014;13:69.CrossRefPubMedCentralPubMed
72.
go back to reference Balestrieri ML, Rizzo MR, Barbieri M, Paolisso P, D’Onofrio N, Giovane A, et al.: Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment. Diabetes. 2014. [epub ahead of print] Balestrieri ML, Rizzo MR, Barbieri M, Paolisso P, D’Onofrio N, Giovane A, et al.: Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment. Diabetes. 2014. [epub ahead of print]
73.
go back to reference Rizzo M, Chandalia M, Patti AM, Di Bartolo V, Rizvi AA, Montalto G, et al. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol. 2014;13:49.CrossRefPubMedCentralPubMed Rizzo M, Chandalia M, Patti AM, Di Bartolo V, Rizvi AA, Montalto G, et al. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol. 2014;13:49.CrossRefPubMedCentralPubMed
74.
go back to reference Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes. 2005;54:146–51.CrossRefPubMed Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes. 2005;54:146–51.CrossRefPubMed
Metadata
Title
Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways
Authors
Lili Shi
Ye Ji
Xiaoyan Jiang
Lihong Zhou
Ying Xu
Yanbo Li
Wei Jiang
Ping Meng
Xiaomin Liu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0177-4

Other articles of this Issue 1/2015

Cardiovascular Diabetology 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.