Effect of atorvastatin on aldosterone production induced by glucose, LDL or angiotensin II in human renal mesangial cells

Tetsuo Nishikawa; Yoko Matsuzawa; Sachiko Suematsu; Jun Saito; Masao Omura; Tomoshige Kino

doi:10.1055/s-0031-1296310

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2010; 60(7): 445-451
DOI: 10.1055/s-0031-1296310

Antidiabetics

Editio Cantor Verlag Aulendorf (Germany)

Effect of atorvastatin on aldosterone production induced by glucose, LDL or angiotensin II in human renal mesangial cells

Tetsuo Nishikawa

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan

,

Yoko Matsuzawa

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan

,

Sachiko Suematsu

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan

,

Jun Saito

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan

,

Masao Omura

¹Department of Medicine, Yokohama Rosai Hospital, Yokohama City, Kanagawa, Japan

,

Tomoshige Kino

²Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

› Author Affiliations

Abstract

Nephropathy is a major complication of diabetes mellitus, thus development of rational therapeutic means is critical for improving public health. It was previously reported that human mesangial cells locally produced aldosterone, a steroid hormone that plays an important role in the development of diabetic nephropathy. The present experiments clarified the effect of glucose, LDL and angiotensin II, the molecules frequently elevated in patients with diabetic nephropathy, on aldosterone production in human primary mesangial cells. These cells expressed the CYP11B2 mRNA, a rate-limiting enzyme in the aldosterone biosynthesis. LDL and angiotensin II stimulated CYP11B2 mRNA expression in these cells, while a high concentration of glucose, angiotensin II and/or LDL increased aldosterone production. Importantly, atorvastatin (CAS 134523-03-8), an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor, strongly suppressed their effects on aldosterone production. Atorvastatin also suppressed positive effects of these compounds on the mRNA expression of the angiotensin II receptor type 1, thus atorvastatin exerted its negative effect in part through changing expression of this receptor. Since elevated levels of glucose and LDL, and increased action of the renin-angiotensin-aldosterone system is known to participate in the progression of diabetic nephropathy, it is speculated that the mesangial endocrine system that produces aldosterone locally is a promising therapeutic target for diabetic nephropathy where HMG-CoA reductase inhibitors provide a beneficial effect.

Key words

Aldosterone - Angiotensin II type 1 receptor - Atorvastatin - CAS 134523-03-8 - CYP11B2 - Mesangial cells

Full Text

References

References
1 Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009; 94: 1853-78
2 Jefferson JA, Shankland SI, Pichler RH. Proteinuria in diabetic kidney disease: a mechanistic viewpoint. Kidney Int. 2008; 74: 22-36
3 Vasudevan MM, Ballantyne CM. Advances in lipid testing and management in diabetics. Endocr Pract. 2009; 1-38
4 Sandhu S, Wiebe N, Fried LF, Tonelli M. Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol. 2006; 17: 2006-16
5 Athyros VG, Papageorgiou AA, Elisaf M, Mikhailidis DP, Group GSC. Statins and renal function in patients with diabetes mellitus. Curr Med Res Opin. 2003; 19: 615-7
6 Jandeleit-Dahm K, Cao Z, Cox AJ, Kelly DJ, Gilbert RE, Cooper ME. Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Kidney Int. 1999; 71 (01) S31-6
7 Blanco S, Vaquero M, Gomez-Guerrero C, Lopez D, Egido J, Romero R. Potential role of angiotensin-converting enzyme inhibitors and statins on early podocyte damage in a model of type 2 diabetes mellitus, obesity, and mild hypertension. Am J Hypertens. 2005; 18: 557-65
8 Zhou MS, Schuman IH, laimes EA, Raij L. Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF-ß, and fibronectin with concomitant increase in nitric oxide bioavailability. Am J Physiol Renal Physiol. 2008; 295: F53-9
9 Schlondorff D, Banas B. The mesangial cell revisited: no cell is an island. J Am Soc Nephrol. 2009; 20: 1179-87
10 Siragy HM, Xue C. Local renal aldosterone production induces inflammation and matrix formation in kidneys of diabetic rats. Exp Physiol. 2008; 93: 817-24
11 Wu O, Liang X, Dai Y, Liu H, Zang Y, Guo Z et al Aldosterone biosynthesis in extra adrenal tissues. Chinese Med J. 1999; 112: 414-8
12 Nishikawa T, Suematsu S, Saito I, Soyama A, Ito H, Kino T et al Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). J Steroid Biochem Mol Biol. 2005; 96: 309-16
13 Martinez D, Oestreicher E, Roubsanthisuk W, Yao T, Ricchiuti V, Williams GK. Angiotensin II, aldosterone, and the caveolae: IV. Aldosterone content of the kidney after adrenalectomy. J Hypertens. 2002; 20: s115 Abstract#P0457
14 Mohaupt MG. The role of adrenal steroidogenesis in arterial hypertension. Endocr Dev. 2008; 13: 133-44
15 Hostetter TH, Rosenberg ME, Ibrahim HN, Juknevicius I. Aldosterone in renal disease. Curr Opin Nephrol Hypertens. 2001; 10: 105-10
16 Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. Clin Invest. 1996; 98: 1063-68
17 Hene RJ, Boer P, Koomans HA, Mees EJ. Plasma aldosterone concentrations in chronic renal disease. Kidney Int. 1982; 21: 98-101
18 Silvestre IS, Heymes C, Oubenaissa A, Robert V, Aupetit-Faisant B, Carayon A et al Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation. 1999; 99: 2694-701
19 Silvestre IS, Robert V, Heymes C, Aupetit-Faisant B, Mouas C, Moalic IM et al Myocardial production of aldosterone and corticosterone in the rat. Physiological regulation. J Biol Chem. 1998; 273: 4883-91
20 Kayes-Wandover KM, White PC. Steroidogenic enzyme gene expression in the human heart. J Clin Endocrinol Metab. 2000; 85: 2519-25
21 Takeda Y, Yoneda T, Demura M, Miyamori I, Mabuchi H. Sodium-induced cardiac aldosterone synthesis causes cardiac hypertrophy. Endocrinology. 2000; 141: 1901-4
22 Bichu P, Nistala. Khan A, Sowers JR, Whaley-Connell A. Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study. Vasc Health Risk Manag. 2009; 5: 129-40
23 Shah IM, Mackay SP, McKay GA. Therapeutic strategies in the treatment of diabetic nephropathy – a translational medicine approach. Curr Med Chem. 2009; 16: 997-1016
24 Hakki T, Bernhardt R. CYP17- and CYPllB-dependent steroid hydroxylases as drug development targets. Pharmacol Ther. 2006; 111: 27-52
25 Hunyady L, Catt KJ. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol. 2006; 20: 953-70
26 Nickenig G, Baumer AT, Temur Y, Kebben D, Jockenhovel F, Bohm M. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation. 1999; 100: 2131-4
27 Wassmann S, Laufs U, Baumer AT, Muller K, Konkol C, Sauer H et al Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol Pharmacol. 2001; 59: 646-54
28 Briones AM, Rodriguez-Criado N, Hernanz R, Garcia-Redondo AB, Rodrigues-Diez RR, Alonso MJ et al Atorvastatin prevents angiotensin II induced vascular remodeling and oxidative stress. Hypertension. 2009; 54: 142-9
29 Maczewski M, Maczewska J, Duda M. Hypercholesterolaemia exacerbates ventricular remodelling after myocardial infarction in the rat: role of angiotensin II type 1 receptors. Br J Pharmacol. 2008; 154: 1640-8
30 Shepherd J, Kastelein TT, Bittner V, Deedwania P, Breazna A, Dobson S et al Treating to New Targets, I., Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol. 2007; 2: 1131-9
31 Taguma Y, Kitamoto Y, Futaki G, Ueda H, Monma H, Ishizaki M et al Effect of captril on heavy proteinuria in azotemic diabetics. N Engl J Med. 1985; 26: 1617-20
32 Brenner BM, Parving HH, Cooper ME, de DZeeuw, Keane WF, Mitch WE et al.; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001; 345: 861-9