Background: Macrophage expression of LpL leads to greater atherosclerosis. Because fatty acids released by LpL are also thought to produce alternatively activated macrophages, we tested whether LpL deletion alters atherosclerosis regression. 

Methods: We treated control LpL floxed (LpLfl/fl) and generalized inducible LpL knockout (iLpL-/-) mice fed an atherogenic diet with low density lipoprotein receptor (LDLR) anti-sense oligonucleotides (ASO). After 16 weeks of ASO treatment, one set of mice was analyzed for baseline lesions, and the remaining mice were treated with sense oligonucleotides to reverse hypercholesterolemia, thereby inducing regression. iLpL-/- mice were treated  with tamoxifen leading to generalized LpL deletion and plasma triglyceride levels of ~500 mg/dl. We also performed an aortic transplant regression study where plaque-rich aortic arches from LDLR knockout mice were transplanted and inter-positioned with the abdominal aortas of recipient mice (LpLfl/fl or iLpL-/- mice). Mice were sacrificed 14 days after the aortic arch transplantation.

Results: After 3 weeks of regression in the LDLR ASO model, lesion size and the macrophage content of lesions (a marker for regression) were similar in LpLfl/fl and              iLpL-/- mice. Similarly, the aortic transplant regression model did not show a difference in macrophage CD68 content in the transplanted aortic arches of recipient LpLfl/fl or iLpL-/- mice. Lesional macrophages isolated using laser capture microdissection from the transplanted arches showed similar expression of inflammatory and anti-inflammatory markers in LpLfl/fl or iLpL-/- mice.  

Conclusion: Hypertriglyceridemia and generalized LpL deletion in mice did not affect atherosclerosis lesion regression in terms of macrophage lesion content.

06 - EFFECT OF LIPOPROTEIN LIPASE (LPL) DELETION ON ATHEROSCLEROSIS REGRESSION