Dataset Information

The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury.

ABSTRACT:

Background

The novel nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone holds promise to be safe and efficient in the treatment of patients with heart failure and/or chronic kidney disease. However, its effects on vascular function remain elusive.

Purpose

The aim of this study was to determine the functional effect of selective MR antagonism by finerenone in vascular cells in vitro and the effect on vascular remodeling following acute vascular injury in vivo.

Methods and results

In vitro, finerenone dose-dependently reduced aldosterone-induced smooth muscle cell (SMC) proliferation, as quantified by BrdU incorporation, and prevented aldosterone-induced endothelial cell (EC) apoptosis, as measured with a flow cytometry based caspase 3/7 activity assay. In vivo, oral application of finerenone resulted in an accelerated re-endothelialization 3 days following electric injury of the murine carotid artery. Furthermore, finerenone treatment inhibited intimal and medial cell proliferation following wire-induced injury of the murine femoral artery 10 days following injury and attenuated neointimal lesion formation 21 days following injury.

Conclusion

Finerenone significantly reduces apoptosis of ECs and simultaneously attenuates SMC proliferation, resulting in accelerated endothelial healing and reduced neointima formation of the injured vessels. Thus, finerenone appears to provide favorable vascular effects through restoring vascular integrity and preventing adverse vascular remodeling.

SUBMITTER: Dutzmann J

PROVIDER: S-EPMC5605005 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury.

Dutzmann Jochen J Musmann Robert-Jonathan RJ Haertlé Marco M Daniel Jan-Marcus JM Sonnenschein Kristina K Schäfer Andreas A Kolkhof Peter P Bauersachs Johann J Sedding Daniel G DG

PloS one 20170919 9

<h4>Background</h4>The novel nonsteroidal mineralocorticoid receptor (MR) antagonist finerenone holds promise to be safe and efficient in the treatment of patients with heart failure and/or chronic kidney disease. However, its effects on vascular function remain elusive.<h4>Purpose</h4>The aim of this study was to determine the functional effect of selective MR antagonism by finerenone in vascular cells in vitro and the effect on vascular remodeling following acute vascular injury in vivo.<h4>Me ...[more]

PMID: 28926607

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Project description:Abstract Background: Data are scant on use of finerenone in diabetic kidney disease (DKD). We undertook this meta-analysis to address this knowledge gap. Methods: Electronic databases were searched for randomized controlled trials (RCTs) involving diabetes patients receiving finerenone compared to controls. The primary outcome was changes in urine albumin-creatinine ratio (UACR). Secondary outcomes were time to kidney failure (decline in GFR by >40% from baseline over 4 weeks), time to end-stage kidney disease, hospitalization for any cause, death and adverse events reported. Results: From initially screened 79 articles, data from 7 RCTs involving 13,783 patients were analyzed (3 in active control group [ACG] defined as having eplerenone/spironolactone as active comparator; 4 in passive control group [PCG] defined as having placebo as controls). Patients receiving finerenone had greater percentage lowering of UACR from baseline as compared to PCG [MD23.82% (95%CI: –24.87 to –22.77); P < 0.01; I2 = 96%] at 90 days, after 2 years [MD 37.9% (95%CI: –38.09 to –37.71); P < 0.01] and 4 years [MD 25.20%(95%CI: –25.63 to –24.77);P < 0.01] of treatment. Patients receiving finerenone has lower chance of >40% decline in GFR (OR 0.83 [95%CI: 0.75 to 0.92];P < 0.01; I2 = 0%). Patients receiving finerenone had lower occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure, as compared to placebo/eplerenone (OR0.86 [95%CI: 0.78 to 0.95]; P = 0.003; I2 = 0%). TAEs was similar (RR0.97 [95%CI: 0.88–1.07]; P = 0.56; I2 = 0%), but SAEs significantly lower (RR0.91 [95%CI: 0.84 to 0.97]; P < 0.01; I2 = 0%) in finerenone-group compared to controls. Conclusion: This meta-analysis provides reassuring data on beneficial impact of finerenone in reducing UACR and GFR decline as compared to placebo. We still lack head-to-head comparison of renal outcomes of finerenone vs eplerenone/spironolactone in DKD.

Dataset Information

The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury.

Background

Purpose

Methods and results

Conclusion

Publications

The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury.

Similar Datasets

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