Peripheral arterial occlusive disease: Global gene expression analyses suggest a major role for immune and inflammatory responses

摘要: Peripheral arterial disease (PAD), a major manifestation of atherosclerosis, is associated with significant cardiovascular morbidity, limb loss and death. However, mechanisms underlying the genesis progression are far from clear. Genome-wide gene expression profiling clinical samples may represent an effective approach to gain relevant information. After histological classification, total 30 femoral artery samples, including 11 intermediate lesions, 14 advanced lesions 5 normal arteries, were profiled using Affymetrix microarray platform. Following real-time RT-PCR validation, different algorithms selection clustering applied identify differentially expressed genes. Under stringent cutoff, i.e., false discovery rate (FDR) <0.5%, we found 366 genes regulated in 447 lesions. Of these, 116 overlapped between 68 up-regulated 48 down-regulated ones. In these genes, immune/inflammatory significantly stages PAD, (85/230 37/172 lesions). Through literature mining pathway analysis databases such as Gene Ontology (GO), Kyoto Encyclopedia Genomics (KEGG), involved responses enriched at PAD(p < 0.05), revealing correlation progression. Moreover, immune-related pathways Toll-like receptor signaling natural killer cell mediated cytotoxicity particularly (P highlighting their pathogenic significance during Lines evidence revealed this study not only support previous hypotheses, primarily based on studies animal models other types disease, that inflammatory influence development but also permit recognition wide spectrum can serve signatures for PAD. Further signature molecules eventually allow us develop more sophisticated protocols pharmaceutical interventions.