Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

Abstract

Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis.

Key words::

• Aging
• cyclo-oxygenase
• nitric oxide
• NO synthase
• platelets
• prostaglandins
• reactive oxygen species

Declaration of interest: This work was supported by NIH grants PO1 HL 068758, R37 HL104017, K08 HL71563, NIH pre-doctoral training grant HL007969-06A1, as well as by NHLBI, National Institutes of Health, Department of Health and Human Services under Contract No. HHSN268201000031C. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the awarding offices. M. M. Bachschmid and S. Schildknecht contributed equally to the writing of the manuscript.