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Endothelial dysfunction and oxidative stress contribute to the atherosclerotic process that includes stiffening of large peripheral arteries. In contrast, our laboratory previously reported a paradoxical increase in cerebrovascular compliance in LDLr(-/-):hApoB(+/+) atherosclerotic (ATX) mice (7). We hypothesized that prevention of cerebral artery endothelial dysfunction with a chronic dietary antioxidant intake would normalize the changes in cerebral artery wall structure and biomechanics and prevent the decline in basal cerebral blood flow associated with atherosclerosis. Three-month-old ATX mice were treated, or not, for 3 mo with the polyphenol (+)-catechin (CAT; 30 mg·kg(-1)·day(-1)) and compared with wild-type controls. In isolated, pressurized cerebral arteries from ATX mice, CAT prevented endothelial dysfunction (deterioration of endothelium-dependent, flow-mediated dilations; P &lt; 0.05), the inward hypertrophic structural remodeling (increase in the wall-to-lumen ratio; P &lt; 0.05), and the rise in cerebrovascular compliance (rightward shift of the stress-strain curve measured in passive conditions, reflecting mechanical properties of the arterial wall; P &lt; 0.05). Doppler optical coherence tomography imaging in vivo confirmed these findings, showing that cerebral compliance was higher in ATX mice and normalized by CAT (P &lt; 0.05). CAT also prevented basal cerebral hypoperfusion in ATX mice (P &lt; 0.05). Active remodeling of the cerebrovascular wall in ATX mice was further suggested by the increase (P &lt; 0.05) in pro-metalloproteinase-9 activity, which was normalized by CAT. We conclude that, by preserving the endothelial function, a chronic treatment with CAT prevents the deleterious effect of severe dyslipidemia on cerebral artery wall structure and biomechanical properties, contributing to preserving resting cerebral blood flow.

american journal of physiology. heart and circulatory physiology

Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr<sup>−/−</sup>:hApoB<sup>+/+</sup> mice and improves cerebral blood flow

Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr−/−:hApoB+/+ mice and improves cerebral blood flow

Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr^−/−:hApoB^+/+ mice and improves cerebral blood flow