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Molecular aspects of atherogenesis: new insights and unsolved questions

  • Published:
Journal of Biomedical Science

Summary

The development of atherosclerotic disease results from the interaction between environment and genetic make up. A key factor in atherogenesis is the oxidative modification of lipids, which is involved in the recruitment of mononuclear leukocytes to the arterial intima – a process regulated by several groups of adhesion molecules and cytokines. Activated leukocytes, as well as endothelial mitochondria, can produce reactive oxygen species (ROS) that are associated with endothelial dysfunction, a cause of reduced nitric oxide (NO) bioactivity and further ROS production. Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) are nuclear receptors significantly involved in the control of lipid metabolism, inflammation and insulin sensitivity. Also, an emerging role has been suggested for G protein coupled receptors and for the small Ras and Rho GTPases in the regulation of the expression of endothelial NO synthase (eNOS) and of tissue factor, which are involved in thrombus formation and modulation of vascular tone. Further, the interactions among eNOS, cholesterol, oxidated LDL and caveola membranes are probably involved in some molecular changes observed in vascular diseases. Despite the relevance of oxidative processes in atherogenesis, anti-oxidants have failed to significantly improve atherosclerosis (ATS) prevention, while statins have proved to be the most successful drugs.

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Authors and Affiliations

  1. Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna – S. Orsola-Malpighi Hospital, Via Albertoni, 15, 40139, Bologna, Italy

    Eleonora Cravero, Antonio Muscari & Paolo Puddu

  2. Department of Internal Medicine and Aging, S. Orsola-Malpighi Hospital, Bologna, Italy

    Giovanni Maria Puddu & Giorgia Arnone

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  1. Giovanni Maria Puddu
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Correspondence to Antonio Muscari.

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Puddu, G., Cravero, E., Arnone, G. et al. Molecular aspects of atherogenesis: new insights and unsolved questions. J Biomed Sci 12, 839–853 (2005). https://doi.org/10.1007/s11373-005-9024-z

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