TY - JOUR
T1 - Oxidation-sensitive mechanisms, vascular apoptosis and atherosclerosis
AU - De Nigris, Filomena
AU - Lerman, Amir
AU - Ignarro, Louis J.
AU - Williams-Ignarro, Sharon
AU - Sica, Vincenzo
AU - Baker, Andrew H.
AU - Lerman, Lilach O.
AU - Geng, Yong J.
AU - Napoli, Claudio
N1 - Funding Information:
All the co-authors contributed to the design of the review. We thank Dr Wulf Palinski (San Diego) for critical comments on the manuscript. Our studies were supported by NIH grants HL-56989, HL-63282, HL-58433 and HL-66999, and by the Mayo Foundation.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Increased generation of oxidants, resulting from disruption of aerobic metabolism and from respiratory burst, is an essential defense mechanism against pathogens and aberrant cells. However, oxidative stress can also trigger and enhance deregulated apoptosis or programmed cell death, characteristic of atherosclerotic lesions. Oxidation-sensitive mechanisms also modulate cellular signaling pathways that regulate vascular expression of cytokines and growth factors, and influence atherogenesis, in particular when increased levels of plasma lipoproteins provide ample substrate for lipid peroxidation and lead to increased formation of adducts with lipoprotein amino acids. In some cases, increased oxidation and apoptosis in a group of cells might be beneficial for survival and function of other groups of arterial cells. However, overall, oxidation and apoptosis appear to promote the progression of diseased arteries towards a lesion that is vulnerable to rupture, and to give rise to myocardial infarction and ischemic stroke. Recent rapid advances in our understanding of the interactions between oxidative stress, apoptosis and arterial gene regulation suggest that selective interventions targeting these biological functions have great therapeutic potential.
AB - Increased generation of oxidants, resulting from disruption of aerobic metabolism and from respiratory burst, is an essential defense mechanism against pathogens and aberrant cells. However, oxidative stress can also trigger and enhance deregulated apoptosis or programmed cell death, characteristic of atherosclerotic lesions. Oxidation-sensitive mechanisms also modulate cellular signaling pathways that regulate vascular expression of cytokines and growth factors, and influence atherogenesis, in particular when increased levels of plasma lipoproteins provide ample substrate for lipid peroxidation and lead to increased formation of adducts with lipoprotein amino acids. In some cases, increased oxidation and apoptosis in a group of cells might be beneficial for survival and function of other groups of arterial cells. However, overall, oxidation and apoptosis appear to promote the progression of diseased arteries towards a lesion that is vulnerable to rupture, and to give rise to myocardial infarction and ischemic stroke. Recent rapid advances in our understanding of the interactions between oxidative stress, apoptosis and arterial gene regulation suggest that selective interventions targeting these biological functions have great therapeutic potential.
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U2 - 10.1016/S1471-4914(03)00139-4
DO - 10.1016/S1471-4914(03)00139-4
M3 - Review article
C2 - 12928037
AN - SCOPUS:0042927973
SN - 1471-4914
VL - 9
SP - 351
EP - 359
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 8
ER -