Abstract 581: Lipid Peroxide Derived Dicarboxylic Acids Induce Atherosclerotic Calcification
Background: Cardiovascular diseases, including atherosclerosis, are the leading cause of death in the United States. Atherosclerotic lesions are formed by deposition of lipids in the intima of arteries. Upon exposure to oxidative stresses, low-density lipoprotein (LDL) is converted to highly atherogenic oxidized LDL (ox-LDL) particles, which contribute to disease development and progression. Advanced disease stages may result in calcification of lesions. This calcification process is important, as it has been shown to be associated with stable plaques that are less prone to rupture. Calcification is present in lipid rich domains of lesions, however neither the composition of the mineralized calcium deposits nor its relationship to lipid peroxidation is known.
Hypothesis: Lipid peroxide derived AZA induces calcification of smooth muscle cells thereby providing the link between calcification and overall plaque burden, and association of calcification with the lipophilic region of the lesion.
Methods: In this study, the potential of lipid peroxide-derived lipophilic dicarboxylic acid (DCA, e.g. azelaic acid) to promote calcification upon exposure to vascular smooth muscle cells was tested. Using 13-Hydroperoxyoctadecadienoic acid (13-hydroperoxylinoleic acid, 13-HPODE) and thin-layer and gas chromatography[[Unable to Display Character: –]]mass spectrometry we characterized the conditions where HPODE is decomposed to aldehyde product 9-oxo-nonanoic acid and its corresponding DCA azelaic acid (AZA).
Results: Both free AZA and intracellular delivery of AZA via lysophosphatidylcholine (lysoPtdCho) micelles induced calcification of aortic smooth muscle cells, as determined by Von Kossa and alizarin red staining. HPODE treatment resulted in the cellular conversion to ONA and AZA as determined by GC-MS.
Conclusion: These results demonstrate that DCAs could contribute to atherosclerotic calcification thus accounting for the latter’s relationship to plaque burden and association with lipids. This study also challenges the dogma that arterial calcification represents the deposition of calcium phosphate. Our future work aims to delineate the association of calcium with lipid rich plaques and lipid oxidation with calcification in animal and human atherosclerosis.
Author Disclosures: A. Riad: None. C.A. Narasimhulu: None. D. Litvinov: None. X. Jiang: None. I.F. Ruiz: None. S. Parthasarathy: None.
- © 2015 by American Heart Association, Inc.