Role of Advanced Glycation End Products with Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic Mice

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2008 May 17

PMID 18483403

Citations 37

Authors

Jun Su

Pamela A Lucchesi

Romer A Gonzalez-Villalobos

Desiree I Palen

Bashir M Rezk

Yasuhiro Suzuki

Hamid A Boulares

Khalid Matrougui

Affiliations

Soon will be listed here.

Abstract

Objective: Type 2 diabetes is associated with increased advanced glycation end product (AGE) formation and vasculopathy. We hypothesized that AGEs contribute to resistance artery dysfunction.

Methods And Results: Type 2 diabetic db(-)/db(-) (diabetic) and nondiabetic db(-)/db(+) (control) mice were treated with the AGE inhibitor (aminoguanidine: 50 mg/Kg/d) for 3 months. Isolated mesenteric resistance arteries (MRAs) were mounted in an arteriograph. Pressure-induced myogenic tone (MT) was increased in diabetic mice but was unaffected by aminoguanidine treatment. Phenylephrine-induced contraction and nitric oxide donor-induced endothelium-independent relaxation were similar in all groups. In diabetic mice, endothelium-dependent relaxation in response to shear-stress or acetylcholine was altered and was associated with reduced eNOS protein and mRNA expression. Aminoguanidine treatment improved endothelial function and restored eNOS expression. AGE formation and hypoxia markers (plasminogen activator inhibitor 1 and Bnip3) were increased in MRA from diabetic mice and normalized with Aminoguanidine. Primary cultured endothelial cells (ECs) isolated from resistance arteries subjected to high glucose for 48 hours showed decreased eNOS expression and phosphorylation in response to calcium ionophore. High glucose decreased antioxidant protein (MnSOD) and increased prooxidant proteins (gp91phox) expression leading to increased oxidative stress generation, as assessed by DHE staining and endothelial NADH/NADPH oxidase activity. The preincubation of ECs with aminoguanidine restored eNOS-phosphorylation and expression as well as the balance between pro- and antioxidant factors induced by high glucose.

Conclusions: We provide evidence of a link between AGEs, oxidative stress, and resistance artery EC dysfunction in type 2 diabetic mice. Thus, AGEs and oxidative stress may be a potential target for overcoming diabetic microvessels complications.

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References

Chen H, Karne R, Hall G, Campia U, Panza J, Cannon 3rd R . High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Am J Physiol Heart Circ Physiol. 2005; 290(1):H137-45. DOI: 10.1152/ajpheart.00768.2005. View

Yamamoto Y, Sakurai S, Watanabe T, Yonekura H, Yamamoto H . [Possible participation of advanced glycation endproducts and their receptor system in the development of diabetic vascular complications]. Nihon Yakurigaku Zasshi. 2003; 121(1):49-55. DOI: 10.1254/fpj.121.49. View

Abularrage C, Sidawy A, Aidinian G, Singh N, Weiswasser J, Arora S . Evaluation of the microcirculation in vascular disease. J Vasc Surg. 2005; 42(3):574-81. DOI: 10.1016/j.jvs.2005.05.019. View

Matrougui K, Loufrani L, Heymes C, Levy B, Henrion D . Activation of AT(2) receptors by endogenous angiotensin II is involved in flow-induced dilation in rat resistance arteries. Hypertension. 1999; 34(4 Pt 1):659-65. DOI: 10.1161/01.hyp.34.4.659. View

A Crackower M, Sarao R, Oudit G, Yagil C, Kozieradzki I, Scanga S . Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002; 417(6891):822-8. DOI: 10.1038/nature00786. View

Sakurai S, Yonekura H, Yamamoto Y, Watanabe T, Tanaka N, Li H . The AGE-RAGE system and diabetic nephropathy. J Am Soc Nephrol. 2003; 14(8 Suppl 3):S259-63. DOI: 10.1097/01.asn.0000077414.59717.74. View

Thornalley P . Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts. Arch Biochem Biophys. 2003; 419(1):31-40. DOI: 10.1016/j.abb.2003.08.013. View

Davis M, Hill M . Signaling mechanisms underlying the vascular myogenic response. Physiol Rev. 1999; 79(2):387-423. DOI: 10.1152/physrev.1999.79.2.387. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

10.

Henrion D, Terzi F, Matrougui K, Duriez M, Boulanger C, Babinet C . Impaired flow-induced dilation in mesenteric resistance arteries from mice lacking vimentin. J Clin Invest. 1998; 100(11):2909-14. PMC: 508498. DOI: 10.1172/JCI119840. View

11.

Schmidt A, Hori O, Brett J, Yan S, Wautier J, Stern D . Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb. 1994; 14(10):1521-8. DOI: 10.1161/01.atv.14.10.1521. View

12.

Ha H, Lee H . Oxidative stress in diabetic nephropathy: basic and clinical information. Curr Diab Rep. 2003; 1(3):282-7. DOI: 10.1007/s11892-001-0047-1. View

13.

Stern D, Yan S, Yan S, Schmidt A . Receptor for advanced glycation endproducts (RAGE) and the complications of diabetes. Ageing Res Rev. 2002; 1(1):1-15. DOI: 10.1016/s0047-6374(01)00366-9. View

14.

Bagi Z, Erdei N, Toth A, Li W, Hintze T, Koller A . Type 2 diabetic mice have increased arteriolar tone and blood pressure: enhanced release of COX-2-derived constrictor prostaglandins. Arterioscler Thromb Vasc Biol. 2005; 25(8):1610-6. DOI: 10.1161/01.ATV.0000172688.26838.9f. View

15.

Belmadani S, Palen D, Gonzalez-Villalobos R, Boulares H, Matrougui K . Elevated epidermal growth factor receptor phosphorylation induces resistance artery dysfunction in diabetic db/db mice. Diabetes. 2008; 57(6):1629-37. PMC: 2758606. DOI: 10.2337/db07-0739. View

16.

Muller J, Davis M, Chilian W . Integrated regulation of pressure and flow in the coronary microcirculation. Cardiovasc Res. 1996; 32(4):668-78. View

17.

Yonekura H, Yamamoto Y, Sakurai S, Watanabe T, Yamamoto H . Roles of the receptor for advanced glycation endproducts in diabetes-induced vascular injury. J Pharmacol Sci. 2005; 97(3):305-11. DOI: 10.1254/jphs.cpj04005x. View

18.

Yonekura H, Yamamoto Y, Sakurai S, Petrova R, Abedin M, Li H . Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2002; 370(Pt 3):1097-109. PMC: 1223244. DOI: 10.1042/BJ20021371. View

19.

Lagaud G, Masih-Khan E, Kai S, van Breemen C, Dube G . Influence of type II diabetes on arterial tone and endothelial function in murine mesenteric resistance arteries. J Vasc Res. 2001; 38(6):578-89. DOI: 10.1159/000051094. View

20.

Pfeiffer A, Spranger J, Meyer-Schwickerath R, Schatz H . Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown. Diabetes. 1997; 46 Suppl 2:S26-30. DOI: 10.2337/diab.46.2.s26. View