Bone metabolism and cardiovascular function update. Impairment of osteo-vascular interaction by glyco-oxidative stress

Abstract

A non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent protein derivatives termed advanced glycation end products (AGE). The formation and accumulation of AGE have been known to progress at a normal physiological aging and at an accelerated rate under diabetes. Recently, the risk of various age-related disorders such as cardiovascular disease, osteoporosis, Alzheimer's disease, and cancer have been reported to increase in patients with diabetes. There is a growing body of evidence that AGE and the receptor RAGE interaction elicits oxidative stress generation and subsequently evoke inflammatory and thrombogenic reactions in a variety of cells, thereby contributing to the progression of these devastating disorders. Further, food- or smoking-derived AGE have also been shown to promote the aging-associated organ damage in humans. These observations suggest that inhibition of the AGE-RAGE-induced oxidative stress generation might be a novel therapeutic target for slowing down the aging process and achieving a successful life. In this paper, we discuss the role of AGE-RAGE-oxidative stress and its therapeutic interventions in osteo-vascular disorders.