title: VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation.
abstract: Metabolic syndrome (MetS) represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF). We hypothesized that very low density lipoproteins (VLDL) in MetS (MetS-VLDL) may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL) and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL), and MetS-VLDL (msVLDL) groups. VLDL (15 µg/g) and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001) at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05). Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. hclee@kmu.edu.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. hclee@kmu.edu.tw.|Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. hclee@kmu.edu.tw.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. hclee@kmu.edu.tw.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. hclee@kmu.edu.tw.
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. hsintinglin2007@gmail.com.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. hsintinglin2007@gmail.com.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. hsintinglin2007@gmail.com.
authors.forename: Hsin-Ting
authors.initials: HT
authors.lastname: Lin
authors.affiliation: Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. kly@cc.kmu.edu.tw.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. kly@cc.kmu.edu.tw.
authors.forename: Liang-Yin
authors.initials: LY
authors.lastname: Ke
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. r00b22042@ntu.edu.tw.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. r00b22042@ntu.edu.tw.
authors.forename: Chi
authors.initials: C
authors.lastname: Wei
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. irpu10.yls@gmail.com.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. irpu10.yls@gmail.com.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. irpu10.yls@gmail.com.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Hsiao
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. jujuson993@gmail.com.|Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. jujuson993@gmail.com.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. jujuson993@gmail.com.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. jujuson993@gmail.com.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. wtlai@kmu.edu.tw.|Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. wtlai@kmu.edu.tw.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. wtlai@kmu.edu.tw.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. wtlai@kmu.edu.tw.
authors.forename: Wen-Ter
authors.initials: WT
authors.lastname: Lai
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. sjshin@kmu.edu.tw.|Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. sjshin@kmu.edu.tw.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. sjshin@kmu.edu.tw.
authors.forename: Shyi-Jang
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. cchen@texasheart.org.|Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchen@texasheart.org.|Vascular and Medicinal Research, Texas Heart Institute, Houston, TX 77030, USA. cchen@texasheart.org.|New York Heart Research Foundation, Mineola, NY 11501, USA. cchen@texasheart.org.|Lipid and Glycoimmune Research Center, Changhua Christian Hospital, Changhua 500, Taiwan. cchen@texasheart.org.
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. sheush@kmu.edu.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. sheush@kmu.edu.tw.|Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. sheush@kmu.edu.tw.
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. binnan@kmu.edu.tw.|Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. binnan@kmu.edu.tw.
authors.forename: Bin-Nan
authors.initials: BN
authors.lastname: Wu
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D003971:Diastole / Q000187:drug effects; D004198:Disease Susceptibility; D050171:Dyslipidemias / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004452:Echocardiography; D005260:Female; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D008079:Lipoproteins, VLDL; D007545:Isoproterenol
keywords: atrial fibrillation; lipotoxicity; metabolic syndrome; very-low-density lipoprotein (VLDL)