Activation of the
mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in
patients with type 2 diabetes, where increased pericellular fibrosis has
emerged as a major contributor. The knowledge of the association between the MR,
fibrosis and the effects of an MR antagonist (MRA) in human adipocytes remains
very limited. The present sub-study including 30 participants was prespecified
as part of the Mineralocorticoid Receptor Antagonist
in type 2 Diabetes (MIRAD) trial, randomizing patients to either high
dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in
fibrosis were evaluated by immunohistological examinations and by the
expression of mRNA and protein markers of fibrosis. Treatment with an MRA
reduced pericellular fibrosis, synthesis of the major subunits of collagen type
I and VI, and the profibrotic factor α-smooth muscle actin, as compared to
placebo in subcutaneous adipose tissue. Furthermore, we found decreased
expression of the MR and downstream molecules neutrophil gelatinase–associated
lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA.
In conclusions, we present original data demonstrating reduced fibrosis in
adipose tissue with inhibition of the MR, which could be a potential
therapeutic approach to prevent the extracellular matrix remodeling of adipose
tissue in type 2 diabetes.
Cardiovascular and Renal Outcomes of Mineralocorticoid Receptor Antagonist Use in PARAGON-HF
