title: Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.
abstract: Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox.
authors.affiliation: Department of neurology, People׳s Hospital of Deyang City, Taishian North Road 173, Deyang City 618000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of neurology, People׳s Hospital of Deyang City, Taishian North Road 173, Deyang City 618000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 Xueyuan Road, Hai Dian District, 100083 Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Qi
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 Xueyuan Road, Hai Dian District, 100083 Beijing, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 Xueyuan Road, Hai Dian District, 100083 Beijing, China. Electronic address: vangeorgeliu@gmail.com.
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of neurology, People׳s Hospital of Deyang City, Taishian North Road 173, Deyang City 618000, China. Electronic address: ronaldnju@gmail.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D015228:Hypertriglyceridemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000502:physiology; D000066829:Neuroprotection / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D020521:Stroke / Q000473:pathology / Q000503:physiopathology*
chemical_list: D053305:Apolipoprotein C-III; C472779:GPI-HBP1 protein, mouse; D018110:Receptors, Lipoprotein
keywords: ApoCIII transgene; Extreme hypertriglyceridemia; GPIHBP1 knockout, transient middle cerebral artery occlusion; Ischemic stroke