title: Advanced atherosclerosis is associated with inflammation, vascular dysfunction and oxidative stress, but not hypertension.
abstract: Although hypertension may involve underlying inflammation, it is unknown whether advanced atherosclerosis - a chronic inflammatory condition - can by itself promote hypertension. We thus tested if advanced atherosclerosis in chronically hypercholesterolemic mice is associated with systemic and end-organ inflammation, vascular dysfunction and oxidative stress, and whether blood pressure is higher than in control mice. Male ApoE-/-and wild-type (C57Bl6J) mice were placed on a high fat or chow diet, respectively, from 5 to 61 weeks of age. Expression of several cytokines (including IL-6, TNF-α, IFN-γ and/or IL-1β) was elevated in plasma, brain, and aorta of ApoE-/-mice. Aortic superoxide production was ∼3.5-fold greater, and endothelium-dependent relaxation was markedly reduced in aorta and mesenteric artery of ApoE-/-versus wild-type mice. There was no difference in blood pressure of aged ApoE-/-(104±3mmHg, n=13) and wild-type mice (113±1mmHg, n=18). To clarify any effects of aging alone, findings from 61 week-old wild-type mice were compared with those from young (8-12 weeks old) chow-fed wild-type mice. The data indicate that aging alone increased renal and aortic expression of numerous cytokines (including CCL2, CCL7 and IL-1β). Aging had no effect on blood pressure, systemic inflammation, oxidative stress or endothelial function. Despite systemic and end-organ inflammation, oxidative stress and endothelial dysfunction, advanced atherosclerosis does not necessarily result in elevated blood pressure.
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: quynh.dinh@monash.edu.
authors.forename: Quynh N
authors.initials: QN
authors.lastname: Dinh
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: s-chrissobolis@onu.edu.
authors.forename: Sophocles
authors.initials: S
authors.lastname: Chrissobolis
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: henry.diep@monash.edu.
authors.forename: Henry
authors.initials: H
authors.lastname: Diep
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: christopher.chan@monash.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Chan
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: dorota.ferens@monash.edu.
authors.forename: Dorota
authors.initials: D
authors.lastname: Ferens
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: grant.drummond@monash.edu.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Australia. Electronic address: chris.sobey@monash.edu.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D001794:Blood Pressure / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D054410:Chemokine CCL7 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007371:Interferon-gamma
keywords: Aging; Atherosclerosis; Endothelial dysfunction; Hypertension; Inflammation; Oxidative stress