Genes Differentially Expressed Across Major Arteries Are Enriched in Endothelial Dysfunction-Related Gene Sets: Implications for Relative Inter-artery Atherosclerosis Risk.

Atherosclerosis differs across major arteries. Although the biological basis is not fully understood, limited evidence of genetic differences has been documented. This study, therefore, was aimed to identify differentially expressed genes between clinically relevant major arteries and investigate their enrichment in endothelial dysfunction-related gene sets. A bioinformatic analysis of publicly available gene-level read counts for coronary, aortic, and tibial arteries was performed. Differential gene expression was conducted with DeSeq2 at a false discovery rate of 0.05. Differentially expressed genes were then subjected to over-representation analysis and active-subnetwork-oriented enrichment analysis, both at a false discovery rate of 0.005. Enriched terms common to both analyses were categorized for each contrast into immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related terms, and the top differentially expressed genes validated against Swiss Institute of Bioinformatics' Bgee database. There was mostly upregulation of differentially expressed genes for the coronary/tibial and aorta/tibial contrasts, but milder changes for the coronary/aorta contrast. Transcriptomic differences between coronary or aortic versus tibial samples largely involved immunity/inflammation-, membrane biology-, lipid metabolism-, and coagulation-related genes, suggesting potential to modulate endothelial dysfunction and atherosclerosis. These results imply atheroprone coronary and aortic environments compared with tibial artery tissue, which may explain observed relative inter-artery atherosclerosis risk.

Impact of the Everolimus-eluting Bioresorbable Scaffold in Coronary Atherosclerosis.

INTRODUCTION AND OBJECTIVES: The Absorb bioresorbable vascular scaffold has been shown to decrease total plaque areas in the treated segment. However, it is unknown whether plaque size is modified in scaffolded segments only or whether the modification extends to other coronary segments. METHODS: Absorb Cohort A is a single-arm, prospective study, with safety and imaging endpoints, in which 30 patients underwent percutaneous coronary intervention with the first generation Absorb bioresorbable vascular scaffold. Noninvasive multislice computed tomography imaging was performed in 18 patients at 18 months and 5 years of follow-up. The present study was an intrapatient comparison of matched segments (normalized by the segment length) of the scaffolded region with nonintervened segments for lumen volume, vessel volume, plaque volume, plaque burden, and percent change in plaque atheroma volume. RESULTS: All 18 scaffolded segments could be analyzed. In the nonintervened segments, 1 of 72 segments had a motion artifact and was excluded. Serial comparison showed that the scaffolded segments showed no significant change in the mean plaque burden, total atheroma volume, total lumen volume, or vessel volume between 18 months and 5 years. Conversely, the untreated segments showed a significant increase in plaque burden (2.7 ± 6.5%; P < .01) and normalized plaque volumes (8.0 ± 22.8mm(3); P < .01). This resulted in a significant difference in plaque burden between scaffolded and nonintervened segments (P = .03). CONCLUSIONS: In this small series, the Absorb bioresorbable vascular scaffold showed the potential to provide an additional benefit to pharmacological therapy in locally reducing progression of percent plaque burden. These findings need to be confirmed in larger studies.