26 December 2017 : Animal Research
Pioglitazone Attenuates Atherosclerosis in Diabetic Mice by Inhibition of Receptor for Advanced Glycation End-Product (RAGE) Signaling
Hongli Gao1ACEF, Hongwei Li23ABG*, Weiping Li23BCD, Xuhua Shen2BDF, Beibing Di1BCFDOI: 10.12659/MSM.907401
Med Sci Monit 2017; 23:6121-6131
Abstract
BACKGROUND: Peroxisome proliferator-activated receptor-g (PPAR-g) exhibits anti-inflammatory and anti-diabetic properties, and is protective against cardiovascular diseases. This study aimed to determine the effects of a PPAR-g agonist pioglitazone on atherogenesis in an ApoE knockout mouse (ApoE–/–) diabetic mouse model and in a cultured vascular smooth muscle cells (VSMCs) model.
MATERIAL AND METHODS: Male ApoE–/– mice were rendered diabetic by 5 daily intraperitoneal injections of streptozotocin. Pioglitazone (20 mg/kg/d) or PPAR-γ inhibitor GW9662 (1 mg/kg/d) were administered for 12 weeks. At the end of treatment, mice were killed and the aortae were isolated. Oil Red O staining was used to evaluate atherosclerotic plaque area. H&E staining was used to evaluate the number of complicated plaques. Western blotting and immunohistochemistry were used to determine the expression of advanced glycation end-products (RAGE) and PPAR-γ. The effects of pioglitazone and GW9662 on RAGE and PPAR-g expression were examined in cultured primary mouse VSMCs in hyperglycemic conditions.
RESULTS: Administration of pioglitazone in diabetic ApoE–/– mice successfully reduced atherosclerotic plaque area and the number of complicated plaques. Moreover, pioglitazone inhibited RAGE and stimulated PPAR-γ protein expression in atherosclerotic plaques of diabetic ApoE–/– mice. In cultured VSMCs upon high-glucose challenge, pioglitazone downregulated RAGE mRNA and protein expression. Blockade of PPAR-γ activity by GW9662 remarkably attenuated the inhibitory actions of pioglitazone on atherogenesis, both in diabetic ApoE–/– mice and in cultured VSMCs, upon high-glucose challenge.
CONCLUSIONS: Pioglitazone has a therapeutic effect on atherosclerosis in diabetes, and inhibition of RAGE signaling plays a critical role in mediating the beneficial effects of pioglitazone.
Keywords: atherosclerosis, Diabetes Mellitus, Muscle, Smooth, Vascular
1299 11
Editorial
01 December 2023 : Editorial
Editorial: Outbreaks of Post-Pandemic Childhood Pneumonia and the Re-Emergence of Endemic Respiratory InfectionsDOI: 10.12659/MSM.943312
Med Sci Monit 2023; 29:e943312
In Press
01 Dec 2023 : Clinical Research
Risk Factors and Clinical Outcomes of COVID-19 Infection in Multiple Sclerosis Patients: A Retrospective St...Med Sci Monit In Press; DOI:
30 Nov 2023 : Review article
Decoding the Neurological Sequelae of General Anesthesia: A ReviewMed Sci Monit In Press; DOI:
30 Nov 2023 : Clinical Research
Enhanced Pain Relief and Muscle Growth in Individuals with Low Back Instability: The Impact of Blood Flow R...Med Sci Monit In Press; DOI:
29 Nov 2023 : Clinical Research
Comparative Analysis of Intramedullary Nail versus Plate Fixation for Fibula Fracture in Supination Externa...Med Sci Monit In Press; DOI:
Most Viewed Current Articles
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292