TBL1XR1 Promotes Coronary Artery Disease by Regulating Triglyceride Metabolism via the PPAR Pathway

Transducin beta-like 1 X-linked receptor 1 (TBL1XR1) is significantly upregulated in the peripheral blood of patients with coronary artery disease (CAD). This study aimed to validate the differential expression of TBL1XR1 in CAD and investigate its role in CAD progression using RNA interference.

The expression of TBL1XR1 at the mRNA and protein levels was detected in patients with CAD and controls using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Additionally, the effects of TBL1XR1 gene silencing in human liver cells through RNA interference on PPARα expression and intracellular triglyceride (TG) levels were determined.

TBL1XR1 expression was significantly higher in the peripheral blood of CAD patients compared to controls at both mRNA (1.71 ± 0.96 vs. 1.00 ± 0.34, p < 0.01) and protein levels (0.41 ± 0.19 vs. 0.13 ± 0.07, p = 0.038). Logistic regression analysis revealed that high TBL1XR1 expression is an independent risk factor for CAD. Relative TBL1XR1 expression positively correlated with serum TG levels (rs = 0.56, p < 0.01) and Gensini score (rs = 0.53, p < 0.01), indicating an association with CAD severity. In human liver cells, TBL1XR1 silencing significantly increased peroxisome proliferator-activated receptor alpha (PPARα) expression at both mRNA (p < 0.05) and protein levels (p < 0.01) while reducing intracellular TG levels (0.24 ± 0.16 vs. 0.51 ± 0.09, p < 0.01).

TBL1XR1 is a key factor for risk assessment, diagnosis, and evaluating coronary lesion severity in patients with CAD. Its role in promoting atherosclerosis initiation and development may be associated with regulation of TG metabolism via the PPARα pathway.