Global gene expression analysis reveals specific patterns of an anti-apoptotic pathway in the atherosclerotic resistant internal thoracic artery

Objectives: The radial artery (RA) is known as an atherosclerotic prone artery in contrast to the atherosclerotic resistant internal thoracic artery (ITA). The aim of the present study was to detect differences in the gene expression profile of both arteries from the same patient.

Methods: Six samples of the distal RA and the distal ITA from six patients undergoing coronary artery bypass grafting have been examined through histomorphometric analysis. Having calculated the morphometric parameters intimal thickness index (ITI), intima to media ratio (IMR) and luminal narrowing (% Ln), a whole genome microarray analysis was performed. The obtained data subsequently underwent pathway analysis to identify biological networks.

Results: The histomorphometric parameters ITI (p<0.03), IMR (p<0.01) and % Ln (p<0.02) were significantly increased in RA compared to ITA. We detected 552 differentially expressed genes between ITA and RA via microarray analysis. An identified biological network for Anti-Apoptosis was selected for further analysis by quantitative RT-PCR, validating the microarray analysis by up-regulation of p21 (11.82-fold, p=0.011), SOCS3 (7.22-fold, p=0.0015), IER3 (4.05-fold, p=0.0475), MCL-1 (2.60-fold, p=0.025) and IL-6 (69.79-fold, p=0.051) in ITA compared to RA (Fig.1).

Fig. 1: Differentially expressed anti-apoptotic genes in the RA relative to the ITA appearing as down-regulated (values of –1 represent no different gene expression in the two arteries).
P-values <0.05 are considered as significant.

Conclusion: The up-regulated anti-apoptotic genes may contribute to the atherosclerotic resistance of the ITA compared to the RA.