Abstract
In addition to hepatic expression, cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are expressed by human macrophages. The combined actions of these proteins have profound effects on HDL structure and function. It is not known how these HDL changes influence atherosclerosis. To elucidate the role of leukocyte-derived HL on atherosclerosis in a background of CETP expression, we studied low density lipoprotein receptor-deficient mice expressing human CETP (CETPtgLDLr -/-) with a leukocyte-derived HL deficiency (HL -/- BM). HL(-/-) bone marrow (BM), CETPtgLDLr(-/-) mice were generated via bone marrow transplantation. Wild-type bone marrow was transplanted into CETPtgLDLr(-/-) mice to generate HL +/+ BM, CETPtgLDLr(-/-) controls. The chimeras were fed a high-fat, high-cholesterol diet for 14 weeks to promote atherosclerosis. In female HL(-/-) BM, CETPtgLDLr(-/-) mice plasma HDL-cholesterol concentration during high-fat feeding was decreased 27% when compared with HL +/+ BM, CETPtgLDLr(-/-) mice (P < 0.05), and this was associated with a 96% increase in en face aortic atherosclerosis (P < 0.05). In male CETPtgLDLr(-/-) mice, leukocyte-derived HL deficiency was associated with a 16% decrease in plasma HDL-cholesterol concentration and a 25% increase in aortic atherosclerosis. Thus, leukocyte-derived HL in CETPtgLDLr(-/-) mice has an atheroprotective role that may involve increased HDL levels.
Highlights
In addition to hepatic expression, cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are expressed by human macrophages
bone marrow transplantation (BMT) were performed in order to examine the influence of leukocyte-derived HL in a background of systemic CETP expression
Atherosclerosis was promoted by highfat feeding in bone marrow (BM) chimeric CETPtgLDLr2/2 mice that either expressed, or were deficient in, leukocyte-derived HL
Summary
In addition to hepatic expression, cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are expressed by human macrophages. To elucidate the role of leukocytederived HL on atherosclerosis in a background of CETP expression, we studied low density lipoprotein receptordeficient mice expressing human CETP (CETPtgLDLr2/2) with a leukocyte-derived HL deficiency (HL2/2 BM). In male CETPtgLDLr2/2 mice, leukocytederived HL deficiency was associated with a 16% decrease in plasma HDL-cholesterol concentration and a 25% increase in aortic atherosclerosis. Leukocyte-derived hepatic lipase increases HDL and decreases en face aortic atherosclerosis in LDLr2/2 mice expressing CETP. Published studies of atherosclerosis-prone mice where expression of either CETP or HL is only leukocyte-derived showed these proteins to be proatherogenic [3, 12]. To examine the influence of leukocyte-derived HL on atherosclerosis in a background of CETP activity, we generated human CETP expressing, low density receptor deficient mice deficient
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
