Hepatic low-density lipoprotein receptor–related protein deficiency in mice increases atherosclerosis independent of plasma cholesterol by Sonia M. S.

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Hepatic low-density lipoprotein receptor–related protein deficiency in mice increases atherosclerosis independent of plasma cholesterol by Sonia M. S. Espirito Santo, Nuno M. M. Pires, Lianne S. M. Boesten, Gery Gerritsen, Niels Bovenschen, Ko Willems van Dijk, J. Wouter Jukema, Hans M. G. Princen, André Bensadoun, Wei-Ping Li, Joachim Herz, Louis M. Havekes, and Bart J. M. van Vlijmen Blood Volume 103(10):3777-3782 May 15, 2004 ©2004 by American Society of Hematology

MX1Cre-mediated recombination of the conditional alleles. MX1Cre-mediated recombination of the conditional alleles. MX1Cre-mediated recombination was determined 12 weeks after pI:pC induction: (1) by detecting β-galactosidase activity on cryosections of liver (A), spleen (B), and aorta (C) of MX1Cre transgenic mice that had been combined with Cre-reporter mice; (2) by immunoblotting membrane proteins isolated from livers of LRPflox/floxLDLR–/–APOE–/– (D, left 2 lanes) and MX1Cre+LRPflox/floxLDLR–/–APOE–/– (D, right 2 lanes) mice and subsequent staining with a polyclonal rabbit anti-LRP; and (3) by immunofluorescent detection of LRP and PDGF receptor in the descending aorta of LRPflox/floxLDLR–/–APOE–/– (E,G) and MX1Cre+LRPflox/floxLDLR–/–APOE–/– (F,H) mice. Sonia M. S. Espirito Santo et al. Blood 2004;103:3777-3782 ©2004 by American Society of Hematology

Lipoprotein distribution. Lipoprotein distribution. Plasma was obtained from uninduced (A,B) and 4-week induced (C,D) LRPflox/floxLDLR–/–APOE–/– (A,C) and MX1Cre+LRPflox/floxLDLR–/–APOE–/– (B,D) mice. Lipoproteins were size-fractionated by FPLC; cholesterol (○) and triglyceride (•) content of the individual fractions was determined. Sonia M. S. Espirito Santo et al. Blood 2004;103:3777-3782 ©2004 by American Society of Hematology

Quantitative assessment of atherosclerosis. Quantitative assessment of atherosclerosis. At 23 weeks after pI:pC induction, the extent of atherosclerosis in LRPflox/floxLDLR–/–APOE–/– (○) or MX1Cre+LRPflox/floxLDLR–/–APOE–/– (•) mice was quantified at the level of the aortic root. Each data point represents the mean lesion area per mouse. Significant differences are indicated; P < .05. Sonia M. S. Espirito Santo et al. Blood 2004;103:3777-3782 ©2004 by American Society of Hematology

Photomicrographs of representative atherosclerotic lesions. Photomicrographs of representative atherosclerotic lesions. Size-matched lesions of LRPflox/floxLDLR–/–APOE–/– (upper panels) and MX1Cre+LRPflox/floxLDLR–/–APOE–/– (lower panels) mice. Sections were stained with either HPS (A-B), the macrophage-specific antibody AIA-31240 (C-D), the SMC–α-actin–specific antibody (E-F), or with Resorcin-Fuchsin (elastin; G-H). Sonia M. S. Espirito Santo et al. Blood 2004;103:3777-3782 ©2004 by American Society of Hematology