title: Catechin prevents severe dyslipidemia-associated changes in wall biomechanics of cerebral arteries in LDLr-/-:hApoB+/+ mice and improves cerebral blood flow.
abstract: 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 < 0.05), the inward hypertrophic structural remodeling (increase in the wall-to-lumen ratio; P < 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 < 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 < 0.05). CAT also prevented basal cerebral hypoperfusion in ATX mice (P < 0.05). Active remodeling of the cerebrovascular wall in ATX mice was further suggested by the increase (P < 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.
authors.affiliation: Université de Montréal, Faculty of Medicine, Departments of Pharmacology, Quebec, Canada.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bolduc
authors.forename: Edward
authors.initials: E
authors.lastname: Baraghis
authors.forename: Natacha
authors.initials: N
authors.lastname: Duquette
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thorin-Trescases
authors.forename: Jean
authors.initials: J
authors.lastname: Lambert
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lesage
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D001696:Biomechanical Phenomena; D002392:Catechin / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003187:Compliance; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004792:Enzyme Precursors / Q000378:metabolism; D005838:Genotype; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D012720:Severity of Illness Index; D013314:Stress, Mechanical; D041623:Tomography, Optical Coherence; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001055:Apolipoproteins B; D004792:Enzyme Precursors; D011973:Receptors, LDL; D002392:Catechin; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9