title: Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort.
abstract: BACKGROUND
  Association of lipoprotein particle size/number and HDL function with mitochondrial oxidative stress and function may underlie the excess cardiovascular (CVD) risk in HIV.
  
  
  RESULTS
  Among HIV infected individuals on stable highly active antiretroviral therapy, we related standard and novel lipid measures [plasma total cholesterol, triglycerides, HDL-C, LDL-C, lipoprotein particle (-P) subclass size and number and HDL function (via cholesterol-efflux capacity)] with oxidative stress [peripheral blood mononuclear cell's mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG)] and function markers [oxidative phosphorylation (OXPHOS) NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activities]. Multivariable-adjusted logistic and linear regression analyses were employed adjusting for age, gender, CD4 nadir, viral load, smoking, diabetes, HOMA-IR, hypertension and lipid medications. Among 150 HIV-infected persons (mean age 52 years, 12% women, median CD4 count 524 cell/mm3), low HDL-C and high total cholesterol/HDL-C ratio were related to PBMC 8-oxo-deoxyguanine (p = 0.01 and 0.02 respectively). Large HDL-P and HDL-P size were inversely related to PBMC 8-oxo-deoxyguanine (p = 0.04). Small LDL-P (p = 0.01) and total LDL-P (p = 0.01) were related to decreased OXPHOS Complex I activity. LDL-P was related to decreased OXPHOS Complex IV activity (p = 0.02). Cholesterol efflux capacity was associated with increased OXPHOS Complex IV activity.
  
  
  CONCLUSIONS
  HDL concentration and particle size and number are related to decreased PBMC mitochondrial oxidative stress whereas HDL function is positively related to mitochondrial oxidative function. The association we find between atherogenic lipoprotein profile and increased oxidative stress and function suggests these pathways may be important in the pathogenesis of cardiometabolic disease in HIV disease.
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; Cardiovascular Division, Department of Medicine, University of California San Francisco, CA, USA. Electronic address: nparikh@medicine.uscf.edu.
authors.forename: Nisha I
authors.initials: NI
authors.lastname: Parikh
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gerschenson
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Bennett
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Louie Mar M
authors.initials: LM
authors.lastname: Gangcuangco
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Mary S
authors.initials: MS
authors.lastname: Lopez
authors.affiliation: Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.affiliation: Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Playford
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA; Department of Neurology, Straub Clinics and Hospital, Honolulu, HI, USA.
authors.forename: Beau K
authors.initials: BK
authors.lastname: Nakamoto
authors.affiliation: Cardiovascular Division, The Queens Medical Center, Honolulu, HI, USA.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Seto
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Chow
authors.affiliation: Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D001786:Blood Glucose; D002784:Cholesterol / Q000097:blood / Q000737:chemistry*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008074:Lipoproteins / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010316:Particle Size; D010766:Phosphorylation
chemical_list: D001786:Blood Glucose; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol; D010100:Oxygen
keywords: Atherosclerosis; Cardiovascular disease; Cholesterol efflux capacity; HDL; Lipids; NMR spectroscopy; Oxidative phosphorylation