Gene expression profiling reveals heterogeneity of perivascular adipose tissues surrounding coronary and internal thoracic arteries

Abstract

The internal thoracic artery (ITA) that differs from coronary artery (CA), rarely develops atherosclerosis. Understanding the mechanism underlying such a difference will help to pave a new way to the prevention and treatment of the disease. We hypothesize herein that the difference in susceptibility to atherosclerosis between CA and ITA is attributable to the heterogeneity of perivascular adipose tissues (PVATs) surrounding these two kinds of arteries, i.e. PVAT-CA and PVAT-ITA. We isolated PVAT from eight patients of coronary heart disease (CHD) and four non-CHD patients. Gene expression patterns were analyzed by using Agilent whole gene expression profile chips. By comparison between PVAT-CA and PVAT-ITA, we identified 2053 differentially expressed genes, of which 1042 were up-regulated and 1011 were down-regulated, respectively, in CHD group. KEGG pathway and gene ontology (GO) analysis revealed that those differentially expressed genes related to inflammation, lipid metabolism and myocardial processes were particularly noted in the CHD group, but not in non-CHD. Several selected genes, including interleukin-1β (IL-1β), interleukin-6 (IL-6), Toll-like receptor 2 (TLR2), Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), serum amyloid A2 (SAA2), and Leptin were validated by real-time PCR analysis. The results showed that the expression levels of IL-1β, IL-6, and Leptin were significantly higher in PVAT-CA than in PVAT-ITA (P = 0.016, 0.021, and 0.018) in CHD patients. Levels of TLR2, TIRAP, and SAA2 expression were also higher in PVAT-CA, however no significant difference was observed (P = 0.054, 0.092, and 0.058). In conclusion, our findings demonstrate differential gene expression patterns between PVAT-CA and PVAT-ITA, revealing a high heterogeneity in PVAT. Particularly, those genes related to inflammation, lipid metabolism and myocardial processes are differentially expressed in PVAT-CA and PVAT-ITA in CHD patients, suggesting an important role of PVAT in the development of coronary atherosclerosis.

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