FUNCTIONAL HIERARCHY OF REMNANT LIPOPROTEIN RECEPTORS

Summary

Principal Investigator: S Fazio
Affiliation: Vanderbilt University
Country: USA
Abstract: DESCRIPTION (provided by applicant): The evolution of the atherosclerotic plaque is regulated by the ability of its cells to dispose of excess cholesterol before apoptosis ensues. Macrophages are the dominant cell type of early plaques in humans and mice, and can utilize several pathways for lipoprotein internalization and for cholesterol efflux. Because cholesterol efflux is activated by delivery of lipoprotein-derived oxysterols to LXR, it is possible that different internalizing receptors may induce different macrophage responses to the same cholesterol load. Apolipoprotein (apo)E, a multifunctional protein highly expressed by macrophages and under LXR control, has strong anti-atherogenic effects that can be mediated by its interactions with internalizing receptors, such LDLR and LRP1, or with agents of cholesterol efflux, such as ABCA1 and PLTP. In the previous cycle of this grant, we discovered that LRP1 deletion from macrophages leads to increased apoE synthesis and, surprisingly, increased lesion formation. This suggests that apoE cannot exert its beneficial effects without LRP1. We also identified a functional interaction between apoE and LRP1 controlling the secretory efficiency of macrophage apoE, and determined that human apoE variants expressed by macrophages associate differently with LRP1 and have profoundly different effects on atherogenesis. Finally, we provided evidence for a role of apoE in macrophage cholesterol efflux even in the presence of excess amounts of apoAI, the canonical activator of the HDL pathway. Our results are compatible with a scenario where apoE and LRP1 work in a functional axis to maximize the adaptive responses of atheroma foam cells to the tremendous cholesterol burden in the arterial intima. In this new proposal, we plan to: 1) Demonstrate that the interaction between apoE and LRP1 in macrophages influences lesion formation in mouse models of atherosclerosis;2) Test the hypothesis that LRP1-mediated internalization of apoE-enriched lipoproteins improves trafficking of cholesterol to efflux- accessible compartments and enhances LXR response;3) Determine whether LRP1 signaling is responsible for anti-inflammatory and pro-survival counter-regulation in macrophages through cholesterol-dependent and independent mechanisms. Our studies aim at unlocking the fundamental regulation of cholesterol release from lesion macrophages into the HDL pathway as a platform for the development of therapeutics for plaque regression and control of ischemic heart disease. Our studies focus on the mechanisms leading to the accumulation and removal of cholesterol from the atherosclerotic plaque, which is the common cause of heart attacks and strokes. Whereas current medications can reduce the accumulation of cholesterol in the plaque by reducing plasma LDL levels, no therapies are available to induce exit of cholesterol from the plaque. We have discovered a functional connection between two proteins (apoE and LRP1) that improves cholesterol disposal in plaque macrophages, and may lead to development of new drugs for regression of coronary plaques.
Funding Period: 1998-01-01 - 2012-07-31
more information: NIH RePORT

Top Publications

  1. pmc Angiotensin-induced abdominal aortic aneurysms in hypercholesterolemic mice: role of serum cholesterol and temporal effects of exposure
    Petra A Prins
    Department of Medicine, Vanderbilt University Medical Center VUMC, Nashville, Tennessee, United States of America
    PLoS ONE 9:e84517. 2014
  2. pmc Putting pleiotropy and selection into context defines a new paradigm for interpreting genetic data
    Irene M Predazzi
    Division of Cardiovascular Medicine, Section of Cardiovascular Disease Prevention, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Circ Cardiovasc Genet 6:299-307. 2013
  3. doi Dysfunctional high-density lipoprotein in patients on chronic hemodialysis
    Suguru Yamamoto
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Am Coll Cardiol 60:2372-9. 2012
  4. pmc Evaluation of macrophage-specific promoters using lentiviral delivery in mice
    M C Levin
    Department of Molecular and Clinical Medicine Wallenberg Laboratory, University of Gothenburg, Goteborg, Sweden
    Gene Ther 19:1041-7. 2012
  5. pmc Selective macrophage ascorbate deficiency suppresses early atherosclerosis
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Free Radic Biol Med 50:27-36. 2011
  6. pmc Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0475, USA
    Arterioscler Thromb Vasc Biol 30:1751-7. 2010
  7. pmc Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt activation
    Patricia G Yancey
    Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Arterioscler Thromb Vasc Biol 30:787-95. 2010
  8. pmc Renal dysfunction potentiates foam cell formation by repressing ABCA1
    Yiqin Zuo
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 2584, USA
    Arterioscler Thromb Vasc Biol 29:1277-82. 2009
  9. pmc Macrophage Mal1 deficiency suppresses atherosclerosis in low-density lipoprotein receptor-null mice by activating peroxisome proliferator-activated receptor-γ-regulated genes
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    Arterioscler Thromb Vasc Biol 31:1283-90. 2011
  10. pmc Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania
    Tanu Rana
    Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee 37208, USA
    J Biol Chem 286:6614-26. 2011

Scientific Experts

  • Vladimir R Babaev
  • Patricia G Yancey
  • Yan Ru Su
  • Uchechukwu K A Sampson
  • L Roberts
  • Alyssa Hasty
  • Sergio Fazio
  • Macrae F Linton
  • Valentina Kon
  • Agnes B Fogo
  • Dwayne E Dove
  • Yiqin Zuo
  • Iekuni Ichikawa
  • Suguru Yamamoto
  • Daping Fan
  • Eisuke Suganuma
  • Nobuhiko Ayabe
  • Michael E Burleigh
  • W Gray Jerome
  • Cheryl D Overton
  • Amy S Major
  • Larry L Swift
  • Petra A Prins
  • Irene M Predazzi
  • Wenwu Zhang
  • M C Levin
  • Ryohei Kaseda
  • Tanu Rana
  • Ashwath Jayagopal
  • Masaru Motojima
  • Shenfeng Qiu
  • Maria Gustafsson
  • Hong Yu
  • Aleksandar K Stanic
  • Jason D Morrow
  • Marnie L Gruen
  • John A Oates
  • June Liu
  • Michael F Hill
  • Hagai Tavori
  • Sam Nwosu
  • DAVID AIREY
  • Prudhvidhar R Perati
  • Giuseppe Novelli
  • Scott M Williams
  • William S Bush
  • Giorgio Sirugo
  • Nicholas D Williams
  • Jonathan L Haines
  • Nathalie Schnetz-Boutaud
  • Antonis Rokas
  • Amos Deinard
  • Alessandra Tacconelli
  • Klaus Friedrich
  • Ayumi Shintani
  • I Gjertsson
  • D R Greaves
  • S O Olofsson
  • S Li
  • U Lidberg
  • M Adiels
  • K Gustafsson
  • Brian Cox
  • T Alp Ikizler
  • S Fazio
  • M F Linton
  • Aihua Bian
  • J Boren
  • P Jirholt
  • A Wramstedt
  • Li Jun Ma
  • Keith T Wilson
  • Anitra L Farrow
  • Gautam Chaudhuri
  • Mukul K Mittal
  • Smita Misra
  • Ian M Willis
  • John L Blakemore
  • Frederick R Haselton
  • Iris Castro
  • Wasif N Khan
  • Wasif Khan
  • Edwin J Weeber
  • Lei Ding
  • Jeanna Perman
  • Vincent Fridén
  • Malin Levin
  • Jan Boren
  • Clay F Semenkovich
  • Pernilla Jirholt

Detail Information

Publications46

  1. pmc Angiotensin-induced abdominal aortic aneurysms in hypercholesterolemic mice: role of serum cholesterol and temporal effects of exposure
    Petra A Prins
    Department of Medicine, Vanderbilt University Medical Center VUMC, Nashville, Tennessee, United States of America
    PLoS ONE 9:e84517. 2014
    ..Thus, we sought insight into the temporal evolution of AAA in apolipoprotein (apo)E(-/-) mice...
  2. pmc Putting pleiotropy and selection into context defines a new paradigm for interpreting genetic data
    Irene M Predazzi
    Division of Cardiovascular Medicine, Section of Cardiovascular Disease Prevention, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Circ Cardiovasc Genet 6:299-307. 2013
    ..We studied patterns of selection in this gene, in humans and nonhuman primates, to determine whether variable selection can lead to conflicting results in cardiovascular disease association studies...
  3. doi Dysfunctional high-density lipoprotein in patients on chronic hemodialysis
    Suguru Yamamoto
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Am Coll Cardiol 60:2372-9. 2012
    ..This study examined the functionality of high-density lipoprotein (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD)...
  4. pmc Evaluation of macrophage-specific promoters using lentiviral delivery in mice
    M C Levin
    Department of Molecular and Clinical Medicine Wallenberg Laboratory, University of Gothenburg, Goteborg, Sweden
    Gene Ther 19:1041-7. 2012
    ..We propose that this is the best currently available MSP to use for directing transgene expression to macrophage populations in vivo using lentiviral vectors...
  5. pmc Selective macrophage ascorbate deficiency suppresses early atherosclerosis
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Free Radic Biol Med 50:27-36. 2011
    ....
  6. pmc Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 0475, USA
    Arterioscler Thromb Vasc Biol 30:1751-7. 2010
    ....
  7. pmc Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt activation
    Patricia G Yancey
    Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Arterioscler Thromb Vasc Biol 30:787-95. 2010
    ..Compared to wild-type macrophage lesions, LRP-1(-/-) lesions had 5.7-fold more necrotic core with more dead cells not associated with macrophages...
  8. pmc Renal dysfunction potentiates foam cell formation by repressing ABCA1
    Yiqin Zuo
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 2584, USA
    Arterioscler Thromb Vasc Biol 29:1277-82. 2009
    ..The mechanisms underlying the heightened risk remain obscure but may relate to differences in CKD-induced atherogenesis, including perturbation of macrophage cholesterol trafficking...
  9. pmc Macrophage Mal1 deficiency suppresses atherosclerosis in low-density lipoprotein receptor-null mice by activating peroxisome proliferator-activated receptor-γ-regulated genes
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    Arterioscler Thromb Vasc Biol 31:1283-90. 2011
    ..Combined deficiency of aP2 and Mal1 has been shown to reduce the development of atherosclerosis, but the independent role of macrophage Mal1 expression in atherogenesis remains unclear...
  10. pmc Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania
    Tanu Rana
    Department of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee 37208, USA
    J Biol Chem 286:6614-26. 2011
    ..Inhibition of PAR1 or calpain 1 in macrophages made them resistant to Leishmania infection. These data suggest that macrophage PAR1 and calpain 1 are potential drug targets against leishmaniasis...
  11. pmc Quantitative estimates of the variability of in vivo sonographic measurements of the mouse aorta for studies of abdominal aortic aneurysms and related arterial diseases
    Uchechukwu K Sampson
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Ultrasound Med 30:773-84. 2011
    ....
  12. pmc Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent
    Patricia G Yancey
    Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, TN 37232, USA
    Circulation 124:454-64. 2011
    ..Thus, our objective was to determine whether the atheroprotective effects of LRP1 require interaction with apoE, one of its ligands with multiple beneficial effects...
  13. pmc Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis
    Suguru Yamamoto
    Department of Pediatrics, Vanderbilt University Medical Center, 1161 21st Avenue South, C 4204 Medical Center North, Nashville, TN 37232 2584, USA
    Arterioscler Thromb Vasc Biol 31:2856-64. 2011
    ..We examined the contribution of macrophage AT1 to accelerated atherosclerosis in an angiotensin II-responsive setting induced by uninephrectomy (UNx)...
  14. ncbi Reduced ABCA1-mediated cholesterol efflux and accelerated atherosclerosis in apolipoprotein E-deficient mice lacking macrophage-derived ACAT1
    Yan Ru Su
    Atherosclerosis Research Unit, Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tenn 37232 6300, USA
    Circulation 111:2373-81. 2005
    ..We have studied the effect of macrophage ACAT1 deletion on atherogenesis in apoE-deficient (apoE-/-) mice with or without the restoration of macrophage apoE...
  15. pmc Lentiviral transduction of apoAI into hematopoietic progenitor cells and macrophages: applications to cell therapy of atherosclerosis
    Yan Ru Su
    Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville TN 37232 6300, USA
    Arterioscler Thromb Vasc Biol 28:1439-46. 2008
    ..We used genetically engineered mouse hematopoietic progenitor cells (HPCs) to investigate the therapeutic effects of human apoAI on atherosclerosis in apoE(-/-) mice...
  16. pmc Self-association of human PCSK9 correlates with its LDLR-degrading activity
    Daping Fan
    Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6300, USA
    Biochemistry 47:1631-9. 2008
    ..These results provide a basis for developing strategies to manipulate PCSK9 activity in the circulation for the treatment of hypercholesterolemia...
  17. pmc The relationship between dose of vitamin E and suppression of oxidative stress in humans
    L Jackson Roberts
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Free Radic Biol Med 43:1388-93. 2007
    ..This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease...
  18. pmc Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice
    June Liu
    Department of Biochemistry and Molecular Biology, East Tennessee State University, Johnson City, TN 37614, USA
    Arterioscler Thromb Vasc Biol 25:174-9. 2005
    ..In this study, we examined the effect of Bax deficiency in bone marrow-derived leukocytes on the development of atherosclerosis in low-density lipoprotein receptor-null (LDLR-/-) mice...
  19. ncbi The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I
    Alyssa H Hasty
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Lipid Res 46:1433-9. 2005
    ..These results suggest that apoE recycling in macrophages may be part of a larger signaling loop activated by HDL and directed at maximizing cholesterol losses from the cell...
  20. ncbi Transiently heightened angiotensin II has distinct effects on atherosclerosis and aneurysm formation in hyperlipidemic mice
    Nobuhiko Ayabe
    Department of Pediatrics, MCN C4204, Vanderbilt University Medical Center, Nashville, TN 37232 2584, USA
    Atherosclerosis 184:312-21. 2006
    ..By contrast, transient AngII-exposure causes prompt aneurysm formation that does not parallel atherosclerosis and disappears even in the face of progressively greater atherosclerotic lesions...
  21. ncbi Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice
    Michael E Burleigh
    Department of Pharmacology, 383 Preston Research Building, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    J Mol Cell Cardiol 39:443-52. 2005
    ..These results are compatible with COX-2 expression by macrophages having a proatherogenic role, and support the potential of anti-inflammatory therapeutic approaches for atherosclerosis...
  22. ncbi ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages
    Dwayne E Dove
    Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    Atherosclerosis 186:267-74. 2006
    ..This change in cholesterol homeostasis may contribute to the atherogenic potential of ACAT1(-/-) macrophages...
  23. ncbi Macrophage apolipoprotein E reduces atherosclerosis and prevents premature death in apolipoprotein E and scavenger receptor-class BI double-knockout mice
    Hong Yu
    Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    Arterioscler Thromb Vasc Biol 26:150-6. 2006
    ..The current study examines the ability of macrophage apoE to improve the dyslipidemia, reduce atherosclerosis, and rescue the lethal phenotype of DKO mice...
  24. ncbi Antiatherogenic effects of angiotensin receptor antagonism in mild renal dysfunction
    Eisuke Suganuma
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    J Am Soc Nephrol 17:433-41. 2006
    ....
  25. pmc Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus
    Aleksandar K Stanic
    Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6300, USA
    Proc Natl Acad Sci U S A 103:7018-23. 2006
    ..Collectively, these studies demonstrate that the lupus-susceptible immune system enhances atherogenesis and modulates plaque composition...
  26. ncbi Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques
    Eisuke Suganuma
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 2584, USA
    J Am Soc Nephrol 18:2311-9. 2007
    ....
  27. ncbi A pathway-dependent on apoE, ApoAI, and ABCA1 determines formation of buoyant high-density lipoprotein by macrophage foam cells
    Patricia G Yancey
    Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn 37232 6300, USA
    Arterioscler Thromb Vasc Biol 27:1123-31. 2007
    ..ABCA1-dependent and ABCA1-independent pathways may operate in high-density lipoprotein formation by macrophages secreting apolipoprotein (apo) E. We examined the impact of ABCA1 on apoE-mediated efflux from cholesterol-enriched macrophages...
  28. ncbi ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages
    Dwayne E Dove
    Department of Pathology, Vanderbilt University Medical Center, Nashville, Tenn 37232 6300, USA
    Arterioscler Thromb Vasc Biol 25:128-34. 2005
    ..The objective of the current study was to elucidate the mechanism of the increased atherosclerosis...
  29. ncbi ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects
    Dwayne E Dove
    Department of Pathology, Vanderbilt University Medical Center, 383 Preston Research Bldg, Nashville, TN 37232 6300, USA
    Am J Physiol Cell Physiol 288:C586-92. 2005
    ..Furthermore, autocrine effects of apoE could be critical in the prevention of foam cell formation in vivo. This novel methodology may be applicable to other types of mixed autocrine/paracrine systems, such as signal transduction systems...
  30. ncbi ACAT inhibition: bad for macrophages, good for smooth muscle cells?
    Sergio Fazio
    Arterioscler Thromb Vasc Biol 25:7-9. 2005
  31. ncbi Retention of low-density lipoprotein in atherosclerotic lesions of the mouse: evidence for a role of lipoprotein lipase
    Maria Gustafsson
    Sahlgrenska Center for Cardiovascular and Metabolic Research Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Goteborg University, Sweden
    Circ Res 101:777-83. 2007
    ..Thus, retention of LDL in the artery wall is initiated by direct LDL-proteoglycan binding but shifts to indirect binding with bridging molecules such as LPL...
  32. ncbi Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    Arterioscler Thromb Vasc Biol 25:1647-53. 2005
    ..Peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in macrophage-derived foam cells of atherosclerotic lesions, and its expression may have a dramatic impact on atherosclerosis...
  33. ncbi Inhibition of cyclooxygenase with indomethacin phenethylamide reduces atherosclerosis in apoE-null mice
    Michael E Burleigh
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6300, USA
    Biochem Pharmacol 70:334-42. 2005
    ....
  34. ncbi Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I
    Marnie L Gruen
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Lipid Res 46:2007-14. 2005
    ..Moreover, the presence of large HDLs without apoA-I provides evidence for an apoA-I-independent pathway of cholesterol efflux, possibly sustained by apoE...
  35. ncbi Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse
    Cheryl D Overton
    Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Circ Res 100:670-7. 2007
    ..Our data support the hypothesis that macrophage LRP modulates atherogenesis through regulation of inflammatory responses...
  36. ncbi Impaired secretion of apolipoprotein E2 from macrophages
    Daping Fan
    Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6300, USA
    J Biol Chem 282:13746-53. 2007
    ..Given the role of locally produced apoE in regulating cholesterol efflux, modulating inflammation, and controlling oxidative stress, this unique property of apoE2 may have important impacts on atherogenesis...
  37. pmc Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6300, USA
    Cell Metab 8:492-501. 2008
    ....
  38. ncbi Cyclooxygenase-1 deficiency in bone marrow cells increases early atherosclerosis in apolipoprotein E- and low-density lipoprotein receptor-null mice
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
    Circulation 113:108-17. 2006
    ..Here, we examined the impact of COX-1 deficiency in bone marrow-derived cells on early atherogenesis in the mouse...
  39. pmc Quantum dot mediated imaging of atherosclerosis
    Ashwath Jayagopal
    Department of Biomedical Engineering, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Nanotechnology 20:165102. 2009
    ..It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression...
  40. ncbi Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI
    Patricia G Yancey
    Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
    J Lipid Res 48:1140-9. 2007
    ..Both factors are likely to contribute to the accelerated atherosclerosis in DKO mice...
  41. ncbi Macrophage expression of peroxisome proliferator-activated receptor-alpha reduces atherosclerosis in low-density lipoprotein receptor-deficient mice
    Vladimir R Babaev
    Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn, USA
    Circulation 116:1404-12. 2007
    ..PPARalpha ligands have been shown to reduce cardiovascular events in high-risk subjects. PPARalpha expression by arterial cells, including macrophages, may exert local antiatherogenic effects independent of plasma lipid changes...