PDF herunterladen
Horm Metab Res 2014; 46(06): 379-383
DOI: 10.1055/s-0033-1361114
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Olmesartan Blocks Advanced Glycation End Products-Induced VCAM-1 Gene Expression in Mesangial Cells by Restoring Angiotensin-Converting Enzyme 2 Level

Y. Ishibashi
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
T. Matsui
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
S. Yamagishi
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 26. September 2013

accepted 07. November 2013

Publikationsdatum:
02. Dezember 2013 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Advanced glycation end products (AGEs) and their receptor (RAGE) system are involved in diabetic nephropathy. Angiotensin-converting enzyme 2 (ACE 2) plays a protective role against cardiovascular and renal injury by stimulating the production of angiotensin-(1–7) [Ang-(1–7)], an antagonist of angiotensin II (Ang II). However, effects of the AGEs-RAGE axis on ACE 2 expression in mesangial cells remain unknown. We examined here the role of ACE 2 in the AGEs-RAGE-induced mesangial cell damage and investigated whether olmesartan, one of the Ang II type 1 receptor blockers (ARB), prevented the deleterious effects of AGEs via restoration of ACE 2 and Ang-(1–7) level. AGEs significantly increased superoxide generation, upregulated RAGE mRNA level, and decreased ACE 2 gene expression and Ang-(1–7) production in mesangial cells, all of which were blocked by olmesartan, but not by a different type of ARB, azilsartan. An antioxidant, N-acetylcysteine or RAGE-antibodies also restored the decrease in ACE 2 mRNA level in AGEs-exposed mesangial cells. Moreover, olmesartan, but not azilsartan completely inhibited the AGEs-induced increase in vascular cell adhesion molecule-1 (VCAM-1) mRNA level in mesangial cells, which was abolished by the treatment with A-779, an antagonist of Ang-(1–7) receptor, Mas receptor. Our present study suggests that olmesartan could block the AGEs-induced VCAM-1 gene induction in mesangial cells by restoring the downregulated ACE 2 levels and subsequently stimulating the Ang-(1–7)-Mas receptor axis. Restoration of ACE 2 levels and blockade of renin-angiotensin system by olmesartan might be a promising strategy for the treatment of diabetic nephropathy.

Key words

AGEs - ACE 2 - Ang-(1–7) - mas receptor
 

  • References

  • 1 Yamagishi S, Imaizumi T. Diabetic vascular complications: pathophysiology, biochemical basis and potential therapeutic strategy. Curr Pharm Des 2005; 11: 2279-2299
    CrossrefPubMedGoogle Scholar
  • 2 Yamagishi S, Matsui T. Nitric oxide, a janus-faced therapeutic target for diabetic microangiopathy-Friend or foe?. Pharmacol Res 2011; 64: 187-194
    CrossrefPubMedGoogle Scholar
  • 3 Remuzzi G, Schieppati A, Ruggenenti P. Clinical practice. Nephropathy in patients with type 2 diabetes. N Engl J Med 2002; 346: 1145-1151
    CrossrefPubMedGoogle Scholar
  • 4 Najafian B, Alpers CE, Fogo AB. Pathology of human diabetic nephropathy. Contrib Nephrol 2011; 170: 36-47
    PubMedGoogle Scholar
  • 5 Stieger N, Worthmann K, Schiffer M. The role of metabolic and haemodynamic factors in podocyte injury in diabetes. Diabetes Metab Res Rev 2011; 27: 207-215
    CrossrefPubMedGoogle Scholar
  • 6 Rahbar S. Novel inhibitors of glycation and AGE formation. Cell Biochem Biophys 2007; 48: 147-157
    CrossrefPubMedGoogle Scholar
  • 7 Stitt AW, Bucala R, Vlassara H. Atherogenesis and advanced glycation: promotion, progression, and prevention. Ann NY Acad Sci 1997; 811: 115-127
    CrossrefPubMedGoogle Scholar
  • 8 D’Agati V, Yan SF, Ramasamy R, Schmidt AM. RAGE, glomerulosclerosis and proteinuria: roles in podocytes and endothelial cells. Trends Endocrinol Metab 2010; 21: 50-56
    CrossrefPubMedGoogle Scholar
  • 9 Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, Watanabe T, Yamagishi S, Sakurai S, Takasawa S, Okamoto H, Yamamoto H. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest 2001; 108: 261-268
    CrossrefPubMedGoogle Scholar
  • 10 Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, Bucciarelli LG, Rong LL, Moser B, Markowitz GS, Stein G, Bierhaus A, Liliensiek B, Arnold B, Nawroth PP, Stern DM, D’Agati VD, Schmidt AM. RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 2003; 162: 1123-1137
    CrossrefPubMedGoogle Scholar
  • 11 Cravedi P, Ruggenenti P, Remuzzi G. Intensified inhibition of renin-angiotensin system: a way to improve renal protection?. Curr Hypertens Rep 2005; 9: 430-436
    CrossrefPubMedGoogle Scholar
  • 12 Yamagishi S, Fukami K, Ueda S, Okuda S. Molecular mechanisms of diabetic nephropathy and its therapeutic intervention. Curr Drug Targets 2007; 8: 952-959
    CrossrefPubMedGoogle Scholar
  • 13 Soldatos G, Cooper ME. Diabetic nephropathy: important pathophysiologic mechanisms. Diabetes Res Clin Pract 2008; 82: S75-S79
    CrossrefPubMedGoogle Scholar
  • 14 Abuissa H, O’Keefe Jr J. The role of renin-angiotensin-aldosterone system-based therapy in diabetes prevention and cardiovascular and renal protection. Diabetes Obes Metab 2008; 10: 1157-1166
    PubMedGoogle Scholar
  • 15 Matsui T, Nishino Y, Maeda S, Takeuchi M, Yamagishi S. Irbesartan inhibits advanced glycation end product (AGE)-induced up-regulation of vascular cell adhesion molecule-1 (VCAM-1) mRNA levels in glomerular endothelial cells. Microvasc Res 2011; 81: 269-273
    CrossrefPubMedGoogle Scholar
  • 16 Fukami K, Yamagishi S, Kaifu K, Matsui T, Kaida Y, Ueda S, Takeuchi M, Asanuma K, Okuda S. Telmisartan inhibits AGE-induced podocyte damage and detachment. Microvasc Res 2013; 88: 79-83
    CrossrefPubMedGoogle Scholar
  • 17 Dilauro M, Burns KD. Angiotensin-(1–7) and its effects in the kidney. Sci World J 2009; 9: 522-535
    CrossrefPubMedGoogle Scholar
  • 18 Agata J, Ura N, Yoshida H, Shinshi Y, Sasaki H, Hyakkoku M, Taniguchi S, Shimamoto K. Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. Hypertens Res 2006; 29: 865-874
    CrossrefPubMedGoogle Scholar
  • 19 Liu CX, Hu Q, Wang Y, Zhang W, Ma ZY, Feng JB, Wang R, Wang XP, Dong B, Gao F, Zhang MX, Zhang Y. Angiotensin-converting enzyme (ACE) 2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy: a comparison with ACE inhibition. Mol Med 2010; 1–2: 59-69
    PubMedGoogle Scholar
  • 20 Yamagishi S, Nakamura K, Matsui T, Inagaki Y, Takenaka K, Jinnouchi Y, Yoshida Y, Matsuura T, Narama I, Motomiya Y, Takeuchi M, Inoue H, Yoshimura A, Bucala R, Imaizumi T. Pigment epithelium-derived factor inhibits advanced glycation end product-induced retinal vascular hyperpermeability by blocking reactive oxygen species-mediated vascular endothelial growth factor expression. J Biol Chem 2006; 281: 20213-20220
    CrossrefPubMedGoogle Scholar
  • 21 Sasaki N, Takeuchi M, Chowei H, Kikuchi S, Hayashi Y, Nakano N, Ikeda H, Yamagishi S, Kitamoto T, Saito T, Makita Z. Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques. Neurosci Lett 2002; 326: 117-120
    CrossrefPubMedGoogle Scholar
  • 22 Ide Y, Matsui T, Ishibashi Y, Takeuchi M, Yamagishi S. Pigment epithelium-derived factor inhibits advanced glycation end product-elicited mesangial cell damage by blocking NF-kappaB activation. Microvasc Res 2010; 80: 227-232
    CrossrefPubMedGoogle Scholar
  • 23 Fukami K, Ueda S, Yamagishi S, Kato S, Inagaki Y, Takeuchi M, Motomiya Y, Bucala R, Iida S, Tamaki K, Imaizumi T, Cooper ME, Okuda S. AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type I receptor interaction. Kidney Int 2004; 66: 2137-2147
    CrossrefPubMedGoogle Scholar
  • 24 Yamagishi S, Matsui T, Nakamura K, Inoue H, Takeuchi M, Ueda S, Okuda S, Imaizumi T. Olmesartan blocks inflammatory reactions in endothelial cells evoked by advanced glycation end products by suppressing generation of reactive oxygen species. Ophthalmic Res 2008; 40: 10-15
    CrossrefPubMedGoogle Scholar
  • 25 Yamagishi S, Matsui T, Nakamura K, Inoue H, Takeuchi M, Ueda S, Fukami K, Okuda S, Imaizumi T. Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in vitro by suppressing receptor for AGEs (RAGE) expression. Microvasc Res 2008; 75: 130-134
    CrossrefPubMedGoogle Scholar
  • 26 Yamagishi S, Takeuchi M, Inoue H. Olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, protects against renal damage in advanced glycation end product (age)-injected rats. Drugs Exp Clin Res 2005; 31: 45-51
    PubMedGoogle Scholar
  • 27 Miyata T, van Ypersele de Strihou C, Ueda Y, Ichimori K, Inagi R, Onogi H, Ishikawa N, Nangaku M, Kurokawa K. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol 2002; 13: 2478-2487
    CrossrefPubMedGoogle Scholar
  • 28 Mire DE, Silfani TN, Pugsley MK. A review of the structural and functional features of olmesartan medoxomil, an angiotensin receptor blocker. J Cardiovasc Pharmacol 2005; 46: 585-593
    CrossrefPubMedGoogle Scholar
  • 29 Fujita M, Okuda H, Tsukamoto O, Asano Y, Hirata YL, Kim J, Miyatsuka T, Takashima S, Minamino T, Tomoike H, Kitakaze M. Blockade of angiotensin II receptors reduces the expression of receptors for advanced glycation end products in human endothelial cells. Arterioscler Thromb Vasc Biol 2006; 26: e138-e142
    CrossrefPubMedGoogle Scholar
  • 30 Iwai M, Horiuchi M. Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1–7)-Mas receptor axis. Hypertens Res 2009; 32: 533-536
    CrossrefPubMedGoogle Scholar
  • 31 Ferrario CM, Varagic J. The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function. Am J Physiol Renal Physiol 2010; 298: F1297-F1305
    CrossrefPubMedGoogle Scholar
  • 32 Rabelo LA, Alenina N, Bader M. ACE2-angiotensin-(1–7)-Mas axis and oxidative stress in cardiovascular disease. Hypertens Res 2011; 34: 154-160
    CrossrefPubMedGoogle Scholar
  • 33 Passos-Silva DG, Verano-Braga T, Santos RA. Angiotensin-(1–7): beyond the cardio-renal actions. Clin Sci (Lond) 2013; 124: 443-456
    CrossrefPubMedGoogle Scholar
  • 34 Ichikawa S, Takayama Y. Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients. Hyperten Res 2001; 24: 641-646
    CrossrefPubMedGoogle Scholar
  • 35 Haller H, Ito S, Izzo Jr JL, Januszewicz A, Katayama S, Menne J, Mimran A, Rabelink TJ, Ritz E, Ruilope LM, Rump LC, Viberti G. ROADMAP Trial Investigators . Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2010; 364: 907-917
    PubMedGoogle Scholar
  • 36 Takeuchi M, Makita Z, Yanagisawa K, Kameda K, Koike T. Detection of noncarboxymethyllysine and carboxymethyllysine advanced glycation end products (AGE) in serum of diabetic patients. Mol Med 1999; 5: 393-405
    PubMedGoogle Scholar
  • 37 Yoshida T, Yamagishi S, Nakamura K, Matsui T, Imaizumi T, Takeuchi M, Koga H, Ueno T, Sata M. Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation. Diabetologia 2006; 49: 3094-3099
    CrossrefPubMedGoogle Scholar
  • 38 Schwocho LR, Masonson HN. Pharmacokinetics of CS-866, a new angiotensin II receptor blocker, in healthy subjects. J Clin Pharmacol 2001; 41: 515-527
    CrossrefPubMedGoogle Scholar