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Free Radic Biol Med. 2019 Nov 25. pii: S0891-5849(19)31574-6. doi: 10.1016/j.freeradbiomed.2019.10.011. [Epub ahead of print]

Role of reactive oxygen species in atherosclerosis: Lessons from murine genetic models.

Author information

1
Inserm U-1048, Université de Toulouse, France. Electronic address: anne.negre-salvayre@inserm.fr.
2
Inserm U-1048, Université de Toulouse, France; Pôle de gynécologie obstétrique, Hôpital Paule-de-Viguier, CHU de Toulouse, France.
3
Inserm U-1048, Université de Toulouse, France.

Abstract

Atherosclerosis is a multifactorial chronic and inflammatory disease of medium and large arteries, and the major cause of cardiovascular morbidity and mortality worldwide. The pathogenesis of atherosclerosis involves a number of risk factors and complex events including hypercholesterolemia, endothelial dysfunction, increased permeability to low density lipoproteins (LDL) and their sequestration on extracellular matrix in the intima of lesion-prone areas. These events promote LDL modifications, particularly by oxidation, which generates acute and chronic inflammatory responses implicated in atherogenesis and lesion progression. Reactive oxygen species (ROS) (which include both free radical and non-free radical oxygen intermediates), play a key-role at each step of atherogenesis, in endothelial dysfunction, LDL oxidation, and inflammatory events involved in the initiation and development of atherosclerosis lesions. Most advanced knowledge supporting the "oxidative theory of atherosclerosis" i.e. the nature and the cellular sources of ROS and antioxidant defences, as well as the mechanisms involved in the redox balance, is based on the use of genetically engineered animals, i.e. transgenic, genetically modified, or altered for systems producing or neutralizing ROS in the vessels. This review summarizes the results obtained from animals genetically manipulated for various sources of ROS or antioxidant defences in the vascular wall, and their relevance (advance or limitation), for understanding the place and role of ROS in atherosclerosis.

KEYWORDS:

Atherosclerosis; Genetic animal models; Lipoxygenases; Mitochondria; Mn-dependent superoxide dismutase; Myeloperoxidase; NADPH oxidase; Nitric oxide synthase; Reactive oxygen species

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