The Effect of Pyridoxamine on Large Artery Stiffening and Brain Oxidative Stress and Inflammation with Age

39 pagesAs people age, large elastic arteries become stiffer and cerebral arteries become dysfunctional. This research sought to determine whether treatment with pyridoxamine, a form of vitamin B6, prevents age-related arterial stiffening by limiting the increases in advanced glycation end products (AGEs), and thereby ameliorates the downstream consequences in cerebral arteries and cerebral cortex by limiting increases in oxidative stress and inflammation. 20 old mice were treated with pyridoxamine for 4 months and pulse wave velocity (PWV), a measure of aortic stiffness, was performed at baseline and every other month. Tissue samples from old control, young control, and old pyridoxamine treated mice were analyzed for gene expression of pro- and antioxidant enzymes and inflammatory cytokines. Aorta samples from each group were analyzed for AGEs by immunofluorescence and for thickness of the arterial wall by Verhoeff Van Gieson staining. Aortic PWV was greater in old control versus young control arteries (306 ± 12 cm/s vs. 273 ± 16 cm/s, p=0.005) however, aortic PWV in pyridoxamine-treated mice did not increase over time (p>0.05). Pyridoxamine did not change AGEs (0.05 ± 0.02 AU) versus old and young control arteries (0.01 ± 0.003 AU vs 0.1 ± 0.05 AU, p=0.10). There was no change to arterial wall structure between groups. In the cerebral cortex, SOD1 trended toward elevation in old pyridoxamine arteries as compared to old controls. IL-1 was significantly increased in old pyridoxamine versus young control (1.0 0.29 AU vs. 3.2 0.60 AU, p=0.03), the same was true in the MCA (1.0 0.29 AU vs. 3.2 0.60 AU, p=0.03). These results suggest that pyridoxamine may reduce arterial stiffening. While previous studies have indicated a reduction in AGEs with pyridoxamine treatment, this was not evident in the present study. Pyridoxamine may increase SOD1 expression, while increases in IL-1 is likely a result of the aging process and not modified by pyridoxamine treatment. Further studies are needed to identify the mechanism by which pyridoxamine prevents age-related arterial stiffening