A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice.

AIM The main pathophysiology of abdominal aortic aneurysm (AAA) considerably overlaps with that of atherosclerosis. We reported that incretins [glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP)] or a dipeptidyl peptidase-4 inhibitor (DPP-4I) suppressed atherosclerosis in apolipoprotein E-null (Apoe－/－) mice. Here we investigated the effects of incretin-related agents on AAA in a mouse model. METHODS Apoe－/－ mice maintained on an atherogenic diet were subcutaneously infused with saline, Ang II (2000 ng/kg/min), Ang II, and native GLP-1 (2.16 nmol/kg/day) or Ang II and native GIP (25 nmol/kg/day) for 4 weeks. DPP-4I (MK0626, 6 mg/kg/day) was provided in the diet to the Ang II-infused mice with or without incretin receptor antagonists [(Pro3) GIP and exendin (9-39)]. RESULTS AAA occurred in 70% of the animals receiving Ang II. DPP-4I reduced this rate to 40% and significantly suppressed AAA dilatation, fibrosis, and thrombosis. In contrast, incretins failed to attenuate AAA. Incretin receptor blockers did not reverse the suppressive effects of DPP-4I on AAA. In the aorta, DPP-4I significantly reduced the expression of Interleukin-1β and increased that of tissue inhibitor of metalloproteinase (TIMP)-2. In addition, DPP-4I increased the ratio of TIMP-2 to matrix metalloproteinases-9. CONCLUSIONS DPP-4I, MK0626, but not native incretins has protective effects against AAA in Ang II-infused Apoe－/－ mice via suppression of inflammation, proteolysis, and fibrosis in the aortic wall.

• Publication year

  2016

• Venue

  Journal of atherosclerosis and thrombosis

• Publication date

  2016-04-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.5551/jat.31997PMID 26549734
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Inflammasome Activation by Mitochondrial Oxidative Stress in Macrophages Leads to the Development of Angiotensin II–Induced Aortic Aneurysm

  2015cited by this paper
• Dipeptidyl Peptidase-4 Inhibitor Decreases Abdominal Aortic Aneurysm Formation through GLP-1-Dependent Monocytic Activity in Mice

  2015cited by this paper
• Dipeptidyl peptidase inhibition prevents diastolic dysfunction and reduces myocardial fibrosis in a mouse model of Western diet induced obesity.

  2014cited by this paper
• Orally administered dipeptidyl peptidase-4 inhibitor (alogliptin) prevents abdominal aortic aneurysm formation through an antioxidant effect in rats.

  2014cited by this paper
• Stromal cell-derived factor-1 promoted angiogenesis and inflammatory cell infiltration in aneurysm walls.

  2014cited by this paper
• Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1β induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes.

  2014cited by this paper
• Stimulation of intestinal growth and function with DPP4 inhibition in a mouse short bowel syndrome model.

  2014cited by this paper
• Pharmacology, physiology, and mechanisms of incretin hormone action.

  2013cited by this paper
• Soluble CD26/Dipeptidyl Peptidase IV Enhances the Transcription of IL-6 and TNF-α in THP-1 Cells and Monocytes

  2013cited by this paper
• Genetic and Pharmacologic Disruption of Interleukin-1&bgr; Signaling Inhibits Experimental Aortic Aneurysm Formation

  2013cited by this paper
• Preventive Effect of Dipeptidyl Peptidase-4 Inhibitor on Atherosclerosis Is Mainly Attributable to Incretin's Actions in Nondiabetic and Diabetic Apolipoprotein E-Null Mice

  2013cited by this paper
• Effects of PKF275-055, a dipeptidyl peptidase-4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E-null mice.

  2012cited by this paper
• Activation of AMP-activated protein kinase α2 by nicotine instigates formation of abdominal aortic aneurysms in mice in vivo

  2012cited by this paper
• Cardiovascular biology of the incretin system.

  2012cited by this paper
• Novel Mechanisms of Abdominal Aortic Aneurysms

  2012cited by this paper
• Tissue inhibitors of metalloproteinases

  2011cited by this paper
• A novel human-based receptor antagonist of sustained action reveals body weight control by endogenous GLP-1.

  2011cited by this paper
• Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice

  2011cited by this paper
• Prolonged infusion of angiotensin II in apoE(-/-) mice promotes macrophage recruitment with continued expansion of abdominal aortic aneurysm.

  2011cited by this paper
• A clinical perspective of IL‐1β as the gatekeeper of inflammation

  2011cited by this paper
• DPP-4 (CD26) Inhibitor Alogliptin Inhibits Atherosclerosis in Diabetic Apolipoprotein E–Deficient Mice

  2011cited by this paper
• Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms.

  2010cited by this paper
• 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.

  2010cited by this paper
• Simvastatin Inhibits Angiotensin II–Induced Abdominal Aortic Aneurysm Formation in Apolipoprotein E–Knockout Mice: Possible Role of ERK

  2009cited by this paper
• SVS practice guidelines for the care of patients with an abdominal aortic aneurysm: executive summary.

  2009cited by this paper
• Mortality of ruptured abdominal aortic aneurysm treated with open or endovascular repair.

  2008cited by this paper
• Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein E-knockout mice

  2008cited by this paper
• p21Cip1 modulates arterial wound repair through the stromal cell-derived factor-1/CXCR4 axis in mice.

  2008cited by this paper
• Suppression of Atherosclerotic Plaque Progression and Instability by Tissue Inhibitor of Metalloproteinase-2: Involvement of Macrophage Migration and Apoptosis

  2006cited by this paper
• Inflammation and cellular immune responses in abdominal aortic aneurysms.

  2006cited by this paper
• Pathophysiology of Abdominal Aortic Aneurysms

  2006cited by this paper
• Abdominal Aortic Aneurysms : Pathophysiological Mechanisms and Clinical Implications

  2004cited by this paper
• SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells.

  2004cited by this paper
• Differential Effects of Doxycycline, a Broad-Spectrum Matrix Metalloproteinase Inhibitor, on Angiotensin II–Induced Atherosclerosis and Abdominal Aortic Aneurysms

  2003cited by this paper
• Aortic Dissection Precedes Formation of Aneurysms and Atherosclerosis in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice

  2003cited by this paper
• Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms.

  2002cited by this paper
• Imaging of abdominal aortic aneurysms.

  2002cited by this paper
• Inflammation in the wall of abdominal aortic aneurysm and its role in the symptomatology of aneurysm.

  2002cited by this paper
• Antagonism of AT2 receptors augments Angiotensin II‐induced abdominal aortic aneurysms and atherosclerosis

  2001cited by this paper
• Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice.

  2000cited by this paper
• Angiotensin II induces nuclear factor- kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway.

  2000cited by this paper
• Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic aneurysms and aortic valves of patients with Marfan's syndrome.

  1998cited by this paper
• Decreased vascular smooth muscle cell density in medial degeneration of human abdominal aortic aneurysms.

  1997cited by this paper
• Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm.

  1997cited by this paper
• High Potency Antagonists of the Pancreatic Glucagon-like Peptide-1 Receptor*

  1997cited by this paper
• Embryonic lineage of vascular smooth muscle cells determines responses to collagen matrices and integrin receptor expression.

  1996cited by this paper
• Increased turnover of collagen in abdominal aortic aneurysms, demonstrated by measuring the concentration of the aminoterminal propeptide of type III procollagen in peripheral and aortal blood samples.

  1995cited by this paper
• Failure of Elastin or Collagen as Possible Critical Connective Tissue Alterations Underlying Aneurysmal Dilatation

  1994cited by this paper
• Cytokines that activate proteolysis are increased in abdominal aortic aneurysms.

  1994cited by this paper
• Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C.

  1993cited by this paper
• Interleukin-1 beta and tumor necrosis factor-alpha release in normal and diseased human infrarenal aortas.

  1992cited by this paper
• Interleukin-1β and tumor necrosis factor-α release in normal and diseased human infrarenal aortas * ** *

  1992cited by this paper

• Therapeutic Strategies for Abdominal Aortic Aneurysm: A Comprehensive Systematic Review

  2025cites this paper
• Medical treatments for abdominal aortic aneurysm: an overview of clinical trials

  2024cites this paper
• Protection of diabetes in aortic abdominal aneurysm: Are antidiabetics the real effectors?

  2023cites this paper
• The influence of dipeptidyl peptidase-4 inhibitor on the progression of type B intramural hematoma

  2022cites this paper
• Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis

  2022cites this paper
• Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of Aortic Aneurysms

  2022cites this paper
• The role of dipeptidyl peptidase-IV in abdominal aortic aneurysm pathogenesis: A systematic review

  2021cites this paper
• Importance of NLRP3 Inflammasome in Abdominal Aortic Aneurysms

  2021cites this paper
• Artesunate Attenuated the Progression of Abdominal Aortic Aneurysm in a Mouse Model.

  2021cites this paper
• Dipeptidyl Peptidase-4 Inhibitor Administration Is Associated with Higher Eosinophil Counts and Batter Clinical Outcomes in Patients with Aorta Intramural Hematoma

  2021cites this paper
• Enhanced Inflammatory Reaction and Thrombosis in High-Fat Diet-Fed ApoE-/- Mice are Attenuated by Celastrol.

  2020cites this paper
• Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes

  2020cites this paper
• The role of IL-1β in aortic aneurysm.

  2020cites this paper
• Effects of Sitagliptin on the Coronary Flow Reserve, Circulating Endothelial Progenitor Cells and Stromal Cell-derived Factor-1alpha

  2019cites this paper
• Introduction to translational research in vascular surgery/medicine

  2019cites this paper
• Diabetes mellitus and abdominal aortic aneurysms: A review of the mechanisms underlying the negative relationship

  2018cites this paper
• Ectopic Expression of PCSK9 by Smooth Muscle Cells Contributes to Aortic Dissection.

  2018cites this paper
• The oral administration of clarithromycin prevents the progression and rupture of aortic aneurysm

  2018cites this paper
• Suppression of Abdominal Aortic Aneurysm Formation in Mice by Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor

  2018cites this paper
• Inhibition of interleukin-1 suppresses angiotensin II-induced aortic inflammation and aneurysm formation.

  2018cites this paper
• Diabetes and aortic aneurysm: current state of the art

  2018cites this paper
• Glucagon-Like peptide-1: A new therapeutic target to treat abdominal aortic aneurysm?

  2018cites this paper
• Clinical advantages and disadvantages of anabolic bone therapies targeting the WNT pathway

  2018cites this paper
• The significance of glucose transporters in the pathogenesis of abdominal aortic aneurysms

  2018cites this paper
• The regulatory role of DPP4 in atherosclerotic disease

  2017cites this paper
• Deletion of hypoxia-inducible factor-1α in myeloid lineage exaggerates angiotensin II-induced formation of abdominal aortic aneurysm.

  2017cites this paper
• Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition

  2017cites this paper
• Combination Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor and a Dipeptidyl Peptidase-4 Inhibitor Additively Suppresses Macrophage Foam Cell Formation and Atherosclerosis in Diabetic Mice

  2017cites this paper
• The role of endothelial nitric oxide in the anti-restenotic effects of liraglutide in a mouse model of restenosis

  2017cites this paper
• Suppressive Effects of Glucose-Dependent Insulinotropic Polypeptide on Cardiac Hypertrophy and Fibrosis in Angiotensin II-Infused Mouse Models.

  2016cites this paper