Arterial Tissue Gene Expression Associated With Telomere Length Attrition in Coronary Artery Disease

Shortened telomere length (TL) in blood cells has been associated with atherosclerotic coronary artery disease (CAD). However, the mechanistic pathways underlying TL attrition in arterial wall tissues of patients with CAD remain unclear.

TL was measured using quantitative polymerase chain reaction in blood granulocytes and matched arterial wall tissues from 155 Chinese men with CAD. RNA sequencing was performed in 34 patients to profile the arterial wall tissue transcriptome. These patients were dichotomized according to the median TL of either arterial wall tissues or granulocytes, and differential gene expression was examined with respect to TL.

No significant correlation was observed between TLs of arterial wall tissues and granulocytes (R=0.107, p=0.19). We identified 10 significant differentially expressed genes (DEGs) associated with TL attrition in arterial wall tissues (false discovery rate [FDR] <0.045), including upregulation of ADRA2A (FDR=0.043), a gene encoding an adrenergic receptor implicated in vasoconstriction of atherosclerotic coronary arteries. Gene-set enrichment analysis also revealed positive enrichment of the vasoconstriction pathway (FDR=0.012) in association with TL attrition at the arterial wall tissue. However, these 10 DEGs were not associated with TL attrition in granulocytes. Instead, TL attrition in granulocytes was linked to negative enrichment of ATP synthesis pathways, potentially reflecting mitochondrial dysfunction.

Our findings suggest that distinct pathway dysfunctions may underlie TL attrition in atherosclerotic arterial walls versus granulocytes, indicating that TL attrition in these compartments could contribute to CAD pathogenesis through different mechanisms.