IS HYPOXIA THE COMMON TRIGGER FOR INFLAMMATION AND APOPTOSIS IN HUMAN CAROTID ATHEROSCLEROTIC PLAQUES?

IS HYPOXIA THE COMMON TRIGGER FOR INFLAMMATION AND APOPTOSIS IN HUMAN CAROTID ATHEROSCLEROTIC PLAQUES? A. Bitto, G. De Caridi, F. Spinelli, F. Squadrito. Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy Introduction: Apoptosis and inflammation are important features of atherosclerotic plaques. Hypoxia inducible factor (HIF-1a) is known to participate in atherosclerosis and to stimulate apoptosis signal-regulating kinase 1 (ASK-1), one of the mitogen-activated protein kinases, which is activated by various extracellular stimuli and involved in a variety of cellular function. Objective: We investigated whether a common signal molecule can trigger these two apparently separate pathways. Patients and Methods: 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-1a expression in carotid specimens. Results: HIF-1a was significantly upregulated in carotid specimens with respect to controls (P < 0.05), 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). Conclusion: Our data suggest that hypoxia is the key regulating factor that triggers inflammation as well as apoptosis in the human atherosclerotic plaque.