Obesity Increases Atherosclerosis Susceptibility via Inter-tissue miR-30e-SLC7A11 Axis

Previous studies showed that microRNA-30e (miR-30e) level is elevated in atherosclerosis and solute carrier family 7 member 11 (SLC7A11), a cystine/glutamate transporter, is involved in atherogenesis. However, whether an endocrine-like link between the adipose-derived miR-30e-5p and SLC7A11 in the vascular endothelium can lead to obesity-caused atherosclerosis is unknown.MiRNA data mining and RT-PCR validations were used to demonstrate the positive association among serum level of miR-30e-5p, obesity, and coronary arterial disease in human patients.

Transcriptomics (bulk RNA-seq and single-nucleus RNA-seq), metabolomics, and in silico analysis were used to establish a miR-30e-5p–SLC7A11 regulation of central carbon metabolism, mitochondrial and endothelial cell (EC) function. Mouse models with EC-specific Slc7a11 knockout (EC-Slc7a11-/-) and gain- or loss-of- function of miR-30e-5p were used to elucidate the detrimental role of this endocrine-like axis in obesity-related atherosclerosis.Our multi-omics approaches demonstrate that the adipose-derived miR-30e-5p downregulated SLC7A11 mRNA in ECs via tissue crosstalk.