Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

Goto, Hiromasa; Nomiyama, Takashi; Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Komiya, Koji; Arakawa, Masayuki; Wen, Jia; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Hirose, Takahisa; Watada, Hirotaka

doi:10.1016/j.bbrc.2010.12.131

Cited by 98 publications

(100 citation statements)

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“…In addition, these agents have potential antiatherosclerotic properties. In a rodent model of atherosclerosis, GLP-1 and GLP-1 receptor agonists were reported to inhibit atherosclerosis and inflammation (6)(7)(8)(9), and DPP-4 inhibitors, including alogliptin, inhibit these pathological processes in GLP-1-dependent and -independent manners (10)(11)(12).…”

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confidence: 99%

Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)

et al. 2015

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OBJECTIVERecent experimental studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1-dependent and -independent manners. The current study investigated the effects of alogliptin, a DPP-4 inhibitor, on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODSThis prospective, randomized, open-label, blinded-end point, multicenter, parallelgroup, comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and randomly allocated to treatment with alogliptin (n = 172) or conventional treatment (n = 169). Primary outcomes were changes in mean common and maximum intima-media thickness (IMT) of the carotid artery measured by carotid arterial echography during a 24-month treatment period. RESULTSAlogliptin treatment had a more potent glucose-lowering effect than the conventional treatment (20.3 6 0.7% vs. 20.1 6 0.8%, P = 0.004) without an increase of hypoglycemia. Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment (20.026 mm [SE 0.009] CONCLUSIONSAlogliptin treatment attenuated the progression of carotid IMT in patients with T2DM free of apparent cardiovascular disease compared with the conventional treatment.

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confidence: 99%

Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)

et al. 2015

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“…The present study also showed that GLP-1 suppressed SMemb-positive VSMCs, a proliferative phenotype that acquires macrophage-like phagocytosis 20 . In previous studies we showed that chronic infusion of GLP-1 significantly prevented the infiltration of reported that exendin-4 suppresses murine VSMC proliferation and reduces intimal thickening after vascular injury 9 . These findings are similar to those of the present study and suggest that incretin-based therapy may be effective for the prevention of atherosclerotic vascular diseases.…”

Section: Discussionmentioning

confidence: 87%

“…Because GLP-1 has suppressive effects on VSMCs, it is likely that these effects are mediated by cAMP generation following activation of GLP-1R. However, Goto et al 9 did not find increased cAMP levels in exendin-4-treated VSMCs. Hattori et al 10 found that activation of GLP-1R induces phosphorylation of AMPactivated protein kinase AMPK independent of adenylate cyclase activity in endothelial cells.…”

Section: Discussionmentioning

confidence: 95%

“…The mechanisms underlying the suppressive effects of incretins on the proliferation and migration of VSMCs remain to be elucidated. Goto et al 9 investigated the molecular mechanisms underlying exendin-4-mediated suppression of VSMCs, however their results did not enable them to reach any definitive conclusions. Because GLP-1 has suppressive effects on VSMCs, it is likely that these effects are mediated by cAMP generation following activation of GLP-1R.…”

Section: Discussionmentioning

confidence: 99%

“…vascular wall and vascular smooth muscle cell VSMC proliferation 8,9 . Liraglutide stimulates nitric oxide production 10 and attenuates tumor necrosis factor--induced oxidative stress and inflammation, as well as the expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and plasminogen activator inhibitor-1 in human umbilical vein endothelial cells 11,12 .…”

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Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

Tomoyasu

Kim‐Kaneyama

Kohashi

et al. 2014

Showa Univ J Med Sci

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: Our group previously demonstrated the suppressive effect of glucagon-like peptide-1 GLP-1 on macrophage-driven atherosclerosis in apolipoprotein E-decient apoE / mice. In the present study we investigated the suppressive effect of GLP-1 on the atherogenic phenotype of vascular smooth muscle cells VSMCs in vivo using apoE / mice, and the proliferation and migration of human VSMCs in vitro. A 4-week infusion of GLP-1 in 17-week-old apoE / mice significantly reduced the proliferative VSMC phenotype stained with SMemb. Platelet-derived growth factor PDGF -BB signi cantly stimulated the proliferation of human aortic VSMCs by three fold. Both 0.1 and 1 nmol / l GLP-1 signi cantly suppressed the PDGF-induced VSMC proliferation, and this suppressive effect was significantly abolished by the GLP-1 receptor antagonist exendin 9−39 50 nmol / l . The GLP-1 receptor agonists liraglutide 100 nmol / l and exendin-4 100 nmol / l mimicked GLP-1, signi cantly suppressing PDGF-induced VSMC proliferation. PDGF-BB signi cantly stimulated the migration of human aortic VSMCs by 1.7 -fold, and this effect was signi cantly suppressed by 1 nmol / l GLP-1. These ndings suggest that GLP-1-related treatments may prevent the progression of atherosclerotic lesions by suppressing the proliferation and migration of VSMCs, which are characteristic features of atherosclerosis.

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Kardiovaskuläre Effekte inkretinbasierter Therapien

Lehrke

2012

Herz

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Pharmacological modulation of the glucagon-like peptide-1 (GLP-1) system has emerged as a new therapeutic option for treatment of diabetes mellitus. In addition to the glucose lowering potential GLP-1 was found to have a variety of cardioprotective effects. GLP-1 reduced the size of myocardial infarction during acute ischemia by activation of prosurvival pathways including PI3-kinase, Akt und ERK1/2. In addition, GLP-1 prevented atherosclerotic lesion formation in experimental models and improved endothelial function while acting anti-inflammatory. Furthermore GLP-1 was found to improve chronic heart failure by increasing insulin independent cellular glucose transport. Consequently GLP-1 based therapies might reduce cardiovascular events in diabetic patients which is currently evaluated in clinical endpoint studies.

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Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

Cited by 98 publications

References 23 publications

Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)

Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)

Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

Kardiovaskuläre Effekte inkretinbasierter Therapien

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