Key result
Increased plasma miRNA-21 levels in young metabolically healthy obese patients were associated with impaired diastolic function and cardiac fibrosis via the TGF-β1/Smad signaling pathway.
Why the study?
Metabolically healthy obese patients account for a large portion of the obese population, but their clinical significance and cardiac dysfunction are often underestimated.
Cross-Sectional (n=612)
Increased plasma miRNA-21 levels in metabolically healthy obese patients are associated with impaired diastolic function and cardiac fibrosis, potentially mediated via the TGF-β1/Smad signaling pathway.
May identify early cardiac involvement in young obese patients; requires prospective validation before clinical use.
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.
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Yang et al. (2020) conducted a cross-sectional in Metabolically healthy obesity (n=612). Elevated miRNA-21 levels vs. Healthy controls and lower miRNA-21 quartiles was evaluated on Diastolic function parameters (E/E' and E/A ratio) and cardiac fibrosis markers. Increased plasma miRNA-21 levels in young metabolically healthy obese patients were associated with impaired diastolic function and cardiac fibrosis via the TGF-β1/Smad signaling pathway.
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