MicroRNA profiles in plasma samples from young metabolically healthy obese patients and miRNA-21 are associated with diastolic dysfunction via TGF-β1/Smad pathway.

BACKGROUND

Metabolically healthy obese patients accounts for a large part of obese population, but its clinical significance and cardiac dysfunction are often underestimated. The microRNA profiles of metabolically healthy obese patients were investigated in the study, and the selected microRNA (miRNA) based on our microarray assay will be further verified in a relatively large metabolically healthy obese population.

METHODS

microRNA microarray was performed from six metabolically healthy obese and 6 health control blood samples. Based on the bioinformatics analysis, we further measured RT-PCR, fibrosis markers, echocardiograms, and TGF-β1/Smad signaling pathway in 600 metabolically healthy obese population.

RESULTS

We found that miRNAs expression characteristics in metabolically healthy obese groups were markedly different from healthy control group. MiRNA-21 was significantly increased in the samples of metabolically healthy obese patients. Besides, miRNA-21 levels were associated with cardiac fibrosis marker. Meanwhile, higher miRNA-21 levels were related to elevated E/E'. Besides, patients with the highest miRNA-21 quartile showed the lowest ratio of E/A. These associations between miRNA-21 and diastolic function parameters were independent of obesity and other confounding variables. Of note, TGF-β1and Smad 3 were significantly upregulated while Smad 7 was downregulated according to the miRNA-21 quartiles in metabolically healthy obese group.

CONCLUSIONS

We demonstrated the profiles of circulating microRNAs in metabolically healthy obese patients. Increased plasma miRNA-21 levels were related to impaired diastolic function independent of other relevant confounding variables. MiRNA-21 could be one of the mechanistic links between obesity and diastolic dysfunction through regulating cardiac fibrosis via TGF-β1/Smad signaling pathway in obese hearts, which may serve as a novel target of disease intervention.