Enhanced Peroxynitrite Formation Is Associated with Vascular Aging

By B. van der Loo, Ralf Labugger, J. Skepper, M. Bachschmid, J. Kilo, J. Powell, M. Palacios-Callender, J. Erusalimsky, T. Quaschning, T. Malinski and 3 more. Journal of Experimental Medicine, 2000

701 citations recorded by the source corpus.

Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-associated enhanced superoxide (·O2 −) production with concomitant quenching of NO by the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels, which also increased with age. Thus, vascular aging appears to be initiated by augmented ·O2 − release, trapping of vasorelaxant NO, and subsequent peroxynitrite formation, followed by the nitration and inhibition of MnSOD. Increased eNOS expression and activity is a compensatory, but eventually futile, mechanism to counter regulate the loss of NO. The ultrastructural distribution of 3-nitrotyrosyl suggests that mitochondrial dysfunction plays a major role in the vascular aging process.

Subfields: Biochemistry, Cardiology and Cardiovascular Medicine, Physiology

View Paper: https://www.semanticscholar.org/paper/543173117fcca32a49bf73bb0d4c2e1207914a34

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. C. Szabó
2. Peter Libby
3. Rafael Radi
4. Guy C. Brown
5. Chris E. Cooper

In Cardiology and Cardiovascular Medicine

1. C. Szabó
2. Peter Libby
3. A. Lichtman
4. I. Tabas

In Physiology

1. Rafael Radi
2. Peter Libby
3. P. Pacher

Citations in the corpus

• Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. (2005, background): “creased 3-nitrotyrosine residues, as noted in our study, represent the footprints of peroxynitrite generation and may lead to inactivation of a number of proteins that may be essential for maintenance of vascular homeostasis.(34) The PM2.”
• Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine (2018, background): “Moreover, peroxynitrite and protein tyrosine nitration participate also in the normal aging process (120, 121).”
• Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol (2006, background): “Although physiological aging is known to be associated with increased oxidative stress in the vasculature (van der Loo et al., 2000; Pacher et al., 2002b; Csiszar et al., 2002), increased XO does not appear to play a major role in the elevated oxidative stress (Csiszar et al., 2002).”
• COVID-19 is, in the end, an endothelial disease (2020, background): “These mechanisms range from impaired nitric oxide synthase expression(19) and/or activity to inactivation of nitric oxide or its conversion to highly prooxidant compounds by encountering pro-oxidant species such as superoxide anion, yielding the potent pro-oxidant peroxynitrate.(20,21) Moreover, the”
• Peroxynitrite, a Stealthy Biological Oxidant* (2013, background): “Peroxynitrite also participates in vascular aging and protein tyrosine nitration of the vessel wall, including the selective nitration and inactivation of prostacyclin synthase (75).”