We tested carotid artery specimens from 50 subjects who underwent angioplasty and five age-matched controls for either Western blot or histologic analysis. The hypoxic status was investigated by means of HIF-1α expression in carotid specimens.
HIF-1α was significantly upregulated in carotid specimens with respect to controls (P < .05), ASK-1 was detected in plaques of any composition from lipidic to calcific, and this expression increased with the stage of the plaque and with the expression of inflammatory (p-ERK, RANK-L, OPG) and apoptotic molecules (caspase 9, p-p-38, and p-JNK).
Our data suggest that hypoxia is the key regulating factor that triggers inflammation as well as apoptosis in the human atherosclerotic plaque.