Glycated albumin induces lipid infiltration in mice aorta independently of DM and RAS local modulation by inducing lipid peroxidation and inflammation

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Gomes, Diego Juvenal ; Velosa, Ana Paula ; Okuda, Ligia Shimabukuro ; Fusco, Fernanda Bueno ; da Silva, Karolinne Santana ; Pinto, Paula Ramos ; Nakandakare, Edna Regina ; Correa-Giannella, Maria Lucia ; Woods, Tom ; Brimble, Margaret Anne ; Pickford, Russell ; Rye, Kerry-Anne ; Teodoro, Walcy Rosolia ; Catanozi, Sergio ; Passarelli, Marisa

• Document type: Journal article
• Source: JOURNAL OF DIABETES AND ITS COMPLICATIONS; v. 30, n. 8, p. 1614-1621, NOV-DEC 2016.
• Web of Science Citations: 2

Abstract

Aims: Advanced glycated albumin (AGE-albumin) adversely impairs macrophage lipid homeostasis in vitro, which may be prevented by angiotensin receptor blockers. In vivo studies are inconclusive whether AGE-albumin itself plays important role in early-stage atherogenesis. We aimed at investigating how AGE-albumin by itself drives atherosclerosis development in dyslipidemic non-diabetic mice and if its effects are due to the activation of renin-angiotensin system in the arterial wall and the expression of genes and proteins involved in lipid flux. Methods and results: Murine albumin glycation was induced by incubation with 10 mM glycolaldehyde and C-albumin with PBS alone. Twelve-week-old-male apoE knockout mice were submitted to a daily IP injection of control (C) or AGE-albumin (2 mg/mL) during 30 days with or without losartan (LOS: 100 mg/L; C + LOS and AGE + LOS). Aortic arch was removed, and gene expression was determined by RT-PCR and protein content by immunofluorescence. Plasma lipid and glucose levels were similar among groups. Systolic blood pressure was similarly reduced in both groups treated with LOS. In comparison to C-albumin, aortic lipid infiltration was 5.3 times increased by AGE-albumin, which was avoided by LOS. LOS prevented the enhancement induced by AGE-albumin in Ager, Tnf and Cybb mRNA levels but did not reduce Olrl. Nfkb and Agt mRNA levels were unchanged by AGE-albumin. LOS similarly reduced Agtri a mRNA level in both C and AGE-albumin groups. In AGE-albumin-treated mice, immunofluorescence for carboxymethyl-lysine, 4-hydroxynonenal and RAGE was respectively, 4.8, 2.6 and 1.7 times enhanced in comparison to C-albumin. These increases were all avoided by LOS. Conclusions: AGE-albumin evokes a pre-stage of atherogenesis in dyslipidemic mice independently of the presence of diabetes mellitus or modulation in the RAS in part by the induction of lipid peroxidation and inflammation. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 13/11084-0 - Chronic sodium chloride restriction and atherogenesis in animal model of dyslipidemia and hypertension
• Grantee: Sergio Catanozi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/04631-0 - Advanced glycation end-products and renin-angiotensin system: impact on the development of atherosclerosis in dislipidemic mice
• Grantee: Diego Juvenal Gomes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/19755-9 - Advanced glycation end products and renin-angiotensin system: impact on the development of atherosclerosis in dyslipidemic mice
• Grantee: Marisa Passarelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/16164-7 - Aortic lipid infiltration in renovascular hypertensive hyperlipidemic mice elicited by dietary sodium chloride restriction improves by losartan and hydralazine
• Grantee: Fernanda Bueno Fusco
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/02854-7 - Anti-inflammatory role of apolipoprotein A-IV in diabetes mellitus and its impact on macrophage reverse cholesterol transport: influence of advanced glycation
• Grantee: Ligia Shimabukuro Okuda
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/23392-1 - Anti-inflammatory function of apolipoprotein A-IV in diabetes mellitus and its effects on reverse cholesterol transport from macrophages: influence of modification by advanced glycation
• Grantee: Ligia Shimabukuro Okuda
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor