Reduction of Atherosclerotic Plaques by Lysosomal Acid Lipase Supplementation

Hong Du, Susan Schiavi, Nick Wan, Mark Levine, David P. Witte, Gregory A. Grabowski

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Objective-Proof of principle is presented for targeted enzyme supplementation by using lysosomal acid lipase to decrease aortic and coronary wall lipid accumulation in a mouse model of atherosclerosis. Methods and Results-Mice with LDL receptor deficiency were placed on an atherogenic diet and developed predictable aortic and coronary atheroma. α -Mannosyl-terminated human lysosomal acid lipase (phLAL) was produced in Pichia pastoris, purified, and administered intravenously to such mice with either early or late lesions. phLAL injections reduced plasma, hepatic, and splenic cholesteryl esters and triglycerides in affected mice. phLAL was detected in hepatic Kupffer cells and in atheromatous foam cells. Repeated enzyme injections were well tolerated, with no obvious adverse effects. In addition, the coronary and aortic atheromatous lesions were (1) eliminated in their early stages and (2) quantitatively and qualitatively reduced in their advanced stages. Conclusion-These results support the potential utility of lysosomal acid lipase supplementation for the treatment of atherosclerosis, a leading cause of mortality and morbidity in Westernized nations.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Sterol Esterase
Atherosclerotic Plaques
Atherosclerosis
Atherogenic Diet
Foam Cells
Injections
Kupffer Cells
Pichia
Cholesterol Esters
LDL Receptors
Enzymes
Hepatocytes
Triglycerides
Morbidity
Lipids
Mortality
Liver

Keywords

  • Atherosclerosis
  • Lesion
  • Lysosomal acid lipase
  • Mice

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Reduction of Atherosclerotic Plaques by Lysosomal Acid Lipase Supplementation. / Du, Hong; Schiavi, Susan; Wan, Nick; Levine, Mark; Witte, David P.; Grabowski, Gregory A.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 1, 01.01.2004, p. 147-154.

Research output: Contribution to journalArticle

Du, Hong ; Schiavi, Susan ; Wan, Nick ; Levine, Mark ; Witte, David P. ; Grabowski, Gregory A. / Reduction of Atherosclerotic Plaques by Lysosomal Acid Lipase Supplementation. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2004 ; Vol. 24, No. 1. pp. 147-154.
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