Aldosterone and the Mineralocorticoid Receptor: Risk Factors for Cardiometabolic Disorders

Overview

Journal Curr Hypertens Rep

Specialty Cardiology & Vascular Diseases

Date 2015 Jun 13

PMID 26068659

Citations 11

Authors

Rajesh Garg

Gail K Adler

Affiliations

Soon will be listed here.

Abstract

Preclinical studies have convincingly demonstrated a role for the mineralocorticoid receptor (MR) in adipose tissue physiology. These studies show that increased MR activation causes adipocyte dysfunction leading to decreased production of insulin-sensitizing products and increased production of inflammatory factors, creating an environment conducive to metabolic and cardiovascular disease. Accumulating data also suggest that MR activation may be an important link between obesity and metabolic syndrome. Moreover, MR activation may mediate the pathogenic consequences of metabolic syndrome. Recent attempts at reversing cardiometabolic damage in patients with type 2 diabetes using MR antagonists have shown promising results. MR antagonists are already used to treat heart failure where their use decreases mortality and morbidity over and above the use of traditional therapies alone. However, more data are needed to establish the benefits of MR antagonists in diabetes, obesity, and metabolic syndrome.

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References

Vaidya A, Underwood P, Hopkins P, Jeunemaitre X, Ferri C, Williams G . Abnormal aldosterone physiology and cardiometabolic risk factors. Hypertension. 2013; 61(4):886-93. PMC: 3615445. DOI: 10.1161/HYPERTENSIONAHA.111.00662. View

Mehdi U, Adams-Huet B, Raskin P, Vega G, Toto R . Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. J Am Soc Nephrol. 2009; 20(12):2641-50. PMC: 2794224. DOI: 10.1681/ASN.2009070737. View

Garg R, Hurwitz S, Williams G, Hopkins P, Adler G . Aldosterone production and insulin resistance in healthy adults. J Clin Endocrinol Metab. 2010; 95(4):1986-90. PMC: 2853992. DOI: 10.1210/jc.2009-2521. View

Chen W, Li F, He C, Zhu Y, Tan W . Elevated prevalence of abnormal glucose metabolism in patients with primary aldosteronism: a meta-analysis. Ir J Med Sci. 2013; 183(2):283-91. DOI: 10.1007/s11845-013-1007-x. View

Dorey R, Pierard C, Shinkaruk S, Tronche C, Chauveau F, Baudonnat M . Membrane mineralocorticoid but not glucocorticoid receptors of the dorsal hippocampus mediate the rapid effects of corticosterone on memory retrieval. Neuropsychopharmacology. 2011; 36(13):2639-49. PMC: 3230488. DOI: 10.1038/npp.2011.152. View

Guo C, Ricchiuti V, Lian B, Yao T, Coutinho P, Romero J . Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation. 2008; 117(17):2253-61. PMC: 2746647. DOI: 10.1161/CIRCULATIONAHA.107.748640. View

Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M . Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab. 2005; 91(2):454-9. DOI: 10.1210/jc.2005-1733. View

Armani A, Cinti F, Marzolla V, Morgan J, Cranston G, Antelmi A . Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high-fat-diet-fed mice. FASEB J. 2014; 28(8):3745-57. DOI: 10.1096/fj.13-245415. View

Buglioni A, Cannone V, Cataliotti A, Sangaralingham S, Heublein D, Scott C . Circulating aldosterone and natriuretic peptides in the general community: relationship to cardiorenal and metabolic disease. Hypertension. 2014; 65(1):45-53. PMC: 4267987. DOI: 10.1161/HYPERTENSIONAHA.114.03936. View

10.

Rogerson F, Yao Y, Young M, Fuller P . Identification and characterization of a ligand-selective mineralocorticoid receptor coactivator. FASEB J. 2014; 28(10):4200-10. DOI: 10.1096/fj.13-242479. View

11.

Baudrand R, Lian C, Lian B, Ricchiuti V, Yao T, Li J . Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity. Nutr Metab Cardiovasc Dis. 2014; 24(1):34-41. PMC: 4405158. DOI: 10.1016/j.numecd.2013.07.004. View

12.

Rossi G, Cesari M, Cuspidi C, Maiolino G, Cicala M, Bisogni V . Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension. 2013; 62(1):62-9. DOI: 10.1161/HYPERTENSIONAHA.113.01316. View

13.

Gomez-Sanchez E, Gomez-Sanchez C . The multifaceted mineralocorticoid receptor. Compr Physiol. 2014; 4(3):965-94. PMC: 4521600. DOI: 10.1002/cphy.c130044. View

14.

Musani S, Vasan R, Bidulescu A, Liu J, Xanthakis V, Sims M . Aldosterone, C-reactive protein, and plasma B-type natriuretic peptide are associated with the development of metabolic syndrome and longitudinal changes in metabolic syndrome components: findings from the Jackson Heart Study. Diabetes Care. 2013; 36(10):3084-92. PMC: 3781556. DOI: 10.2337/dc12-2562. View

15.

Stomby A, Andrew R, Walker B, Olsson T . Tissue-specific dysregulation of cortisol regeneration by 11βHSD1 in obesity: has it promised too much?. Diabetologia. 2014; 57(6):1100-10. DOI: 10.1007/s00125-014-3228-6. View

16.

Rossignol P, Dobre D, McMurray J, Swedberg K, Krum H, Van Veldhuisen D . Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy:.... Circ Heart Fail. 2013; 7(1):51-8. DOI: 10.1161/CIRCHEARTFAILURE.113.000792. View

17.

Garg R, Kneen L, Williams G, Adler G . Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects. Diabetes Obes Metab. 2013; 16(3):268-72. PMC: 3946356. DOI: 10.1111/dom.12224. View

18.

Schafer N, Lohmann C, Winnik S, Van Tits L, Miranda M, Vergopoulos A . Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity. Eur Heart J. 2013; 34(45):3515-24. PMC: 3844149. DOI: 10.1093/eurheartj/eht095. View

19.

Kuhn E, Bourgeois C, Keo V, Viengchareun S, Muscat A, Meduri G . Paradoxical resistance to high-fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor-overexpressing mice. Am J Physiol Endocrinol Metab. 2013; 306(1):E75-90. DOI: 10.1152/ajpendo.00323.2013. View

20.

Pfeffer M, Claggett B, Assmann S, Boineau R, Anand I, Clausell N . Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. Circulation. 2014; 131(1):34-42. DOI: 10.1161/CIRCULATIONAHA.114.013255. View