Lipoprotein lipase increases lipoprotein binding to the artery wall and increases endothelial layer permeability by formation of lipolysis products

John C Rutledge, Mable M. Woo, Allen A. Rezai, Linda K. Curtiss, Ira J. Goldberg

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and efflux were separately determined. Perfusion of arteries with buffer plus lipoprotein lipase (LpL) increased LDL accumulation 5-fold (0.1±0.03 mV/min [control] versus 0.5±0.05 mV/min [LpL]) by increasing LDL retention in the artery wall. This effect was blocked by heparin and monoclonal antibodies directed against the amino-terminal region of apolipoprotein B (apo B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effect of hydrolysis of triglyceride-rich lipoproteins on endothelial barrier function was studied. We compared endothelial layer permeability using a water-soluble reference molecule, fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma, dextran accumulation within the artery wall increased >4-fold (0.024±0.01 mV/min [control] versus 0.098±0.05 mV/min [LpL]). Under the same conditions, LpL increased LDL accumulation ≃3-fold (0.016±0.003 mV/min [control] versus 0.047±0.013 mV/min [LpL]). Rapid efflux of LDL from the artery wall indicated that increased endothelial layer permeability was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the amount of LDL in the artery wall. These findings may pertain to the observed relationship between increased postprandial lipemia and atherosclerosis.

Original languageEnglish (US)
Pages (from-to)819-828
Number of pages10
JournalCirculation Research
Volume80
Issue number6
StatePublished - 1997

Keywords

  • artery
  • atherosclerosis
  • low-density lipoprotein
  • proteoglycan
  • triglyceride

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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