Mineralocorticoid receptor throughout the vessel: a key to vascular dysfunction in obesity

Abstract

This editorial refers to ‘Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity’[†][1], by N. Schafer et al. , on page 3515 Obesity is a highly prevalent chronic condition and a major risk factor for several metabolic and cardiovascular (CV) diseases. Numerous human studies have demonstrated that obesity is associated with hypertension and vascular dysfunction secondary to arterial stiffness, reduced endothelium-dependent relaxation, and atherosclerosis.1 The exact mechanisms implicated in obesity-related vascular dysfunction have not been fully elucidated, but are likely to involve a complex interplay between multiple endocrine and paracrine factors, inflammation, oxidative stress, and structural modifications of the vessel. In recent years there has been a growing interest in the simultaneous worldwide increase in the prevalence of obesity, hypertension, and hyperaldosteronism, and a possible inter-relationship between these conditions. The relevance of aldosterone to human health is supported by prospective studies demonstrating a positive correlation between plasma levels of aldosterone and CV mortality.2 Further, pivotal clinical trials have shown that mineralocorticoid receptor (MR) antagonists, such as spironolactone or eplerenone, markedly improve morbidity and mortality in heart failure.3 We and others have shown that obesity is associated with increased aldosterone production in humans and increased aldosterone and MR levels in obese diabetic mice.4,5 MR blockade improved the proinflammatory cytokine profiles of adipose tissue in the obese mice. These findings led to the hypothesis that elevated aldosterone levels contribute to CV injury, progression of atherosclerosis, and metabolic disorders in obesity ( Figure 1 ). The specific mechanisms for CV injury may be related to aldosterone's renal effects to promote sodium retention and volume expansion as well as to MR activation in multiple extrarenal tissues, including the heart, vasculature, monocytes/macrophages, and adipose tissue. Specifically in vessels, aldosterone and/or MR activation increases vascular macrophage infiltration, enhances the proinflammatory cytokine profile, … [1]: #fn-2