The Effect of Large Artery Stiffness on Cognitive Decline, Inflammation, and Oxidative Stress

44 pagesStiffer large elastic arteries are a consequence of advancing age and are associated with cognitive impairment. Recent studies in young mice have shown that even short-term exposure to increased large artery stiffness leads to cerebrovascular dysfunction. However, the direct effects of long-term exposure to increased large artery stiffness are unknown. Therefore, this study looked at the combination of age and large artery stiffness on cognitive function, cerebrovascular function, inflammation, and oxidative stress. Old elastin haploinsufficient mice with large artery stiffness did not have impaired memory and motor coordination compared to both young and old controls. However, old elastin haploinsufficient mice had impaired cerebral artery endothelial function due to lower nitric oxide bioavailability. Old wildtype mice had higher levels of inflammation in the entorhinal cortex, hippocampus, and thalamus than young mice, while elastin haploinsufficient mice trended towards having higher levels of inflammation in the entorhinal cortex than control mice. Finally, old elastin haploinsufficent mice have more endothelial nitric oxide synthase uncoupling in the cerebral artery compared to control mice, indicating a greater likelihood of oxidative stress. These results suggest that while large artery stiffness leads to impaired cerebral artery endothelial function, increased oxidative stress, and increased inflammation, it does not lead to cognitive decline