This protocol enabled the procurement of fasting human plasma for isolation of lipoproteins. The cellular effects and chemistry of modified lipoproteins - both oxidized and aggregated - were studied. Oxidized low density lipoproteins (oxLDL) were known to be toxic to a variety of cell types, but relatively little was known about the toxic effects of oxLDL on vascular smooth muscle cells (SMC). We found that LDL oxidized by incubation with 5 fM cupric ions was toxic to cultured porcine SMC when administered at concentrations of 25 fg protein/ml and higher. The toxicity was demonstrated whether cells were proliferating or not, and was most evident in the presence of 0.4% lipoprotein-deficient serum - characteristics distinct from the toxicity of iron-oxidized LDL for cultured fibroblasts. Inhibition of a-hydroxy-a-methylglutaryl CoA reductase was hypothesized as a mechanism of toxicity, but mevalonic acid, the product of this enzyme, failed to protect against the toxicity of either oxLDL or the pure oxysterols. Alpha-tocopherol, alpha-tocopherol acetate, probucol, butylated hydroxytoluene, and deferoxamine provided partial protection to SMC exposed to oxLDL. These results suggested a role for newly initiated lipid peroxidation in the development of toxicity. Results were published in Atherosclerosis.

Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
James, Jennifer; Munson, David; DeMauro, Sara B et al. (2017) Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support. J Pediatr 190:118-123.e4
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Archer, Stephanie Wilson; Carlo, Waldemar A; Truog, William E et al. (2016) Improving publication rates in a collaborative clinical trials research network. Semin Perinatol 40:410-417
Ahmed, Zuhayer; Prasad, Indrajit; Rahman, Hafizur et al. (2016) A Male with Extreme Subcutaneous Insulin Resistance: A Case Report. Rom J Diabetes Nutr Metab Dis 23:209-213
Phelps, Dale L; Ward, Robert M; Williams, Rick L et al. (2016) Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 80:209-17
Barroso, Julie; Leserman, Jane; Harmon, James L et al. (2015) Fatigue in HIV-Infected People: A Three-Year Observational Study. J Pain Symptom Manage 50:69-79
Stafford-Smith, Mark; Li, Yi-Ju; Mathew, Joseph P et al. (2015) Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci. Kidney Int 88:823-32

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