Profile

Research in Dr. Linton's laboratory focuses on the areas of lipoprotein metabolism and atherosclerosis. A major focus is the investigation of the role of the macrophage in atherosclerosis. The first recognizable lesion of atherosclerosis is the fatty streak which consists primarily of cholesterol loaded macrophages or foam cells. The macrophage expresses genes for a number of lipoprotein receptors, apoproteins, enzymes, and cytokines that may influence foam cell formation and atherogenesis. Since tissue macrophages are derived from monocytes, bone marrow transplantation in gene targeted mice is being used to deliver genetically altered macrophages to the atherosclerotic lesion, providing an in vivo model in which to examine the role of expression of various candidate genes by the macrophage in atherogenesis. Recent studies have focused on the role of apolipoprotein (apo) E secretion by the macrophage in the pathogenesis of atherosclerosis. ApoE is a ligand for receptor mediated lipoprotein clearance, and studies in Dr. Linton's laboratory have demonstrated that expression of apoE by the macrophage in the artery wall is a protective mechanism that retards foam cell formation and atherosclerosis. Gene transfer studies are in progress to investigate the potential of the macrophage as a vehicle for cellular gene therapy of atherosclerotic lesions.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Macrophage apoAI protects against dyslipidemia-induced dermatitis and atherosclerosis without affecting HDL. Tavori H, Su YR, Yancey PG, Giunzioni I, Wilhelm AJ, Blakemore JL, Zabalawi M, Linton MF, Sorci-Thomas MG, Fazio S (2015) J Lipid Res 56(3): 635-43
    › Primary publication · 25593328 (PubMed) · PMC4340310 (PubMed Central)
  2. Dysfunctional high-density lipoproteins in children with chronic kidney disease. Kaseda R, Jabs K, Hunley TE, Jones D, Bian A, Allen RM, Vickers KC, Yancey PG, Linton MF, Fazio S, Kon V (2015) Metabolism 64(2): 263-73
    › Primary publication · 25467845 (PubMed) · PMC4277938 (PubMed Central)
  3. Identification of small proline-rich repeat protein 3 as a novel atheroprotective factor that promotes adaptive Akt signaling in vascular smooth muscle cells. Segedy AK, Pyle AL, Li B, Zhang Y, Babaev VR, Jat P, Fazio S, Atkinson JB, Linton MF, Young PP (2014) Arterioscler Thromb Vasc Biol 34(12): 2527-36
    › Primary publication · 25278290 (PubMed) · PMC4239161 (PubMed Central)
  4. Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice. Babaev VR, Hebron KE, Wiese CB, Toth CL, Ding L, Zhang Y, May JM, Fazio S, Vickers KC, Linton MF (2014) J Lipid Res 55(11): 2296-308
    › Primary publication · 25240046 (PubMed) · PMC4617132 (PubMed Central)
  5. Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice. Tavori H, Fan D, Giunzioni I, Zhu L, Linton MF, Fogo AB, Fazio S (2014) J Lipid Res 55(10): 2073-81
    › Primary publication · 25183802 (PubMed) · PMC4174000 (PubMed Central)
  6. Proprotein convertase subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B lipoproteins through both low-density lipoprotein receptor-dependent and -independent mechanisms. Rashid S, Tavori H, Brown PE, Linton MF, He J, Giunzioni I, Fazio S (2014) Circulation 130(5): 431-41
    › Primary publication · 25070550 (PubMed) · PMC4115295 (PubMed Central)
  7. Response to Duell et al. Tavori H, Giunzioni I, Linton MF, Fazio S (2014) Circ Res 115(1): e5
    › Primary publication · 24951770 (PubMed)
  8. Association of soy food intake with risk and biomarkers of coronary heart disease in Chinese men. Yu D, Zhang X, Xiang YB, Yang G, Li H, Fazio S, Linton M, Cai Q, Zheng W, Gao YT, Shu XO (2014) Int J Cardiol 172(2): e285-7
    › Primary publication · 24438928 (PubMed) · PMC3947738 (PubMed Central)
  9. Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis. Tavori H, Giunzioni I, Linton MF, Fazio S (2013) Circ Res 113(12): 1290-5
    › Primary publication · 24122718 (PubMed) · PMC3939022 (PubMed Central)
  10. Oral retinoids and plasma lipids. Lilley JS, Linton MF, Fazio S (2013) Dermatol Ther 26(5): 404-10
    › Primary publication · 24099071 (PubMed)
  11. Killing two birds with one stone, maybe: CETP inhibition increases both high-density lipoprotein levels and insulin secretion. Fazio S, Linton MF (2013) Circ Res 113(2): 94-6
    › Primary publication · 23833288 (PubMed) · PMC3953452 (PubMed Central)
  12. Genetic abnormalities in apolipoprotein B. Young SG, Linton MF (1991) Trends Cardiovasc Med 1(2): 59-65
    › Primary publication · 21239331 (PubMed)
  13. Murine bone marrow transplantation as a novel approach to studying the role of macrophages in lipoprotein metabolism and atherogenesis. Fazio S, Linton MF (1996) Trends Cardiovasc Med 6(2): 58-65
    › Primary publication · 21232276 (PubMed)
  14. Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease. Lewis TL, Cao D, Lu H, Mans RA, Su YR, Jungbauer L, Linton MF, Fazio S, LaDu MJ, Li L (2010) J Biol Chem 285(47): 36958-68
    › Primary publication · 20847045 (PubMed) · PMC2978624 (PubMed Central)
  15. 6-Mercaptopurine, monocytes, and atherosclerosis. Linton MF, Fazio S (2010) Arterioscler Thromb Vasc Biol 30(8): 1494-6
    › Primary publication · 20631345 (PubMed) · PMC2922006 (PubMed Central)
  16. Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice. Babaev VR, Li L, Shah S, Fazio S, Linton MF, May JM (2010) Arterioscler Thromb Vasc Biol 30(9): 1751-7
    › Primary publication · 20558818 (PubMed) · PMC2924448 (PubMed Central)
  17. Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis. Chung CP, Oeser A, Raggi P, Sokka T, Pincus T, Solus JF, Linton MF, Fazio S, Stein CM (2010) J Rheumatol 37(8): 1633-8
    › Primary publication · 20516025 (PubMed) · PMC2914215 (PubMed Central)
  18. Insights into atherosclerosis using nanotechnology. Jayagopal A, Linton MF, Fazio S, Haselton FR (2010) Curr Atheroscler Rep 12(3): 209-15
    › Primary publication · 20425261 (PubMed) · PMC2863145 (PubMed Central)
  19. Prevalence and determinants of hyperuricemia in middle-aged, urban Chinese men. Villegas R, Xiang YB, Cai Q, Fazio S, Linton M, Li H, Elasy T, Zheng W, Shu XO (2010) Metab Syndr Relat Disord 8(3): 263-70
    › Primary publication · 20158446 (PubMed) · PMC3136729 (PubMed Central)
  20. Macrophage LRP-1 controls plaque cellularity by regulating efferocytosis and Akt activation. Yancey PG, Blakemore J, Ding L, Fan D, Overton CD, Zhang Y, Linton MF, Fazio S (2010) Arterioscler Thromb Vasc Biol 30(4): 787-95
    › Primary publication · 20150557 (PubMed) · PMC2845445 (PubMed Central)
  21. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Erbay E, Babaev VR, Mayers JR, Makowski L, Charles KN, Snitow ME, Fazio S, Wiest MM, Watkins SM, Linton MF, Hotamisligil GS (2009) Nat Med 15(12): 1383-91
    › Primary publication · 19966778 (PubMed) · PMC2790330 (PubMed Central)
  22. Renal dysfunction potentiates foam cell formation by repressing ABCA1. Zuo Y, Yancey P, Castro I, Khan WN, Khan W, Motojima M, Ichikawa I, Fogo AB, Linton MF, Fazio S, Kon V (2009) Arterioscler Thromb Vasc Biol 29(9): 1277-82
    › Primary publication · 19667109 (PubMed) · PMC2748735 (PubMed Central)
  23. Fenofibrate and risk of minor amputations in diabetes. Fazio S, Linton MF (2009) Lancet 373(9677): 1740-1
    › Primary publication · 19465214 (PubMed)
  24. Quantum dot mediated imaging of atherosclerosis. Jayagopal A, Su YR, Blakemore JL, Linton MF, Fazio S, Haselton FR (2009) Nanotechnology 20(16): 165102
    › Primary publication · 19420562 (PubMed) · PMC2718756 (PubMed Central)
  25. Elevated high-density lipoprotein (HDL) levels due to hepatic lipase mutations do not reduce cardiovascular disease risk: another strike against the HDL dogma. Fazio S, Linton MF (2009) J Clin Endocrinol Metab 94(4): 1081-3
    › Primary publication · 19349471 (PubMed) · PMC2682471 (PubMed Central)
  26. Cyclooxygenase products and atherosclerosis. Linton MF, Fazio S (2008) Drug Discov Today Ther Strateg 5(1): 25-36
    › Primary publication · 19343100 (PubMed) · PMC2630286 (PubMed Central)
  27. Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis. Babaev VR, Chew JD, Ding L, Davis S, Breyer MD, Breyer RM, Oates JA, Fazio S, Linton MF (2008) Cell Metab 8(6): 492-501
    › Primary publication · 19041765 (PubMed) · PMC2614698 (PubMed Central)
  28. Prevalence and determinants of metabolic syndrome according to three definitions in middle-aged Chinese men. Villegas R, Xiang YB, Yang G, Cai Q, Fazio S, Linton MF, Elasy T, Xu WH, Li H, Cai H, Gao YT, Zheng W, Shu XO (2009) Metab Syndr Relat Disord 7(1): 37-45
    › Primary publication · 19032041 (PubMed) · PMC3135894 (PubMed Central)
  29. Regulation of tumor necrosis factor receptor-1 and the IKK-NF-kappaB pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor. Gaultier A, Arandjelovic S, Niessen S, Overton CD, Linton MF, Fazio S, Campana WM, Cravatt BF, Gonias SL (2008) Blood 111(11): 5316-25
    › Primary publication · 18369152 (PubMed) · PMC2396725 (PubMed Central)
  30. Retention of low-density lipoprotein in atherosclerotic lesions of the mouse: evidence for a role of lipoprotein lipase. Gustafsson M, Levin M, Skålén K, Perman J, Fridén V, Jirholt P, Olofsson SO, Fazio S, Linton MF, Semenkovich CF, Olivecrona G, Borén J (2007) Circ Res 101(8): 777-83
    › Primary publication · 17761930 (PubMed)
  31. A new age of discovery for plasma lipoproteins. Fazio S, Linton MF (2007) Curr Opin Lipidol 18(4): 387-8
    › Primary publication · 17620853 (PubMed)
  32. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS (2007) Nature 447(7147): 959-65
    › Primary publication · 17554340 (PubMed) · PMC4076119 (PubMed Central)
  33. Sorting out the complexities of reverse cholesterol transport: CETP polymorphisms, HDL, and coronary disease. Fazio S, Linton MF (2006) J Clin Endocrinol Metab 91(9): 3273-5
    › Primary publication · 16960121 (PubMed)
  34. Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. Baumgartl J, Baudler S, Scherner M, Babaev V, Makowski L, Suttles J, McDuffie M, Tobe K, Kadowaki T, Fazio S, Kahn CR, Hotamisligil GS, Krone W, Linton M, Brüning JC (2006) Cell Metab 3(4): 247-56
    › Primary publication · 16581002 (PubMed) · PMC4027059 (PubMed Central)
  35. Failure of ACAT inhibition to retard atherosclerosis. Fazio S, Linton M (2006) N Engl J Med 354(12): 1307-9
    › Primary publication · 16554534 (PubMed)
  36. Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages. Freeman NE, Rusinol AE, Linton M, Hachey DL, Fazio S, Sinensky MS, Thewke D (2005) J Lipid Res 46(9): 1933-43
    › Primary publication · 15995174 (PubMed) · PMC2768430 (PubMed Central)
  37. Interplay between apolipoprotein E and scavenger receptor class B type I controls coronary atherosclerosis and lifespan in the mouse. Fazio S, Linton MF (2005) Circulation 111(25): 3349-51
    › Primary publication · 15983260 (PubMed)
  38. ACAT inhibition: bad for macrophages, good for smooth muscle cells? Fazio S, Dove DE, Linton MF (2005) Arterioscler Thromb Vasc Biol 25(1): 7-9
    › Primary publication · 15626766 (PubMed)
  39. Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice. Liu J, Thewke DP, Su YR, Linton MF, Fazio S, Sinensky MS (2005) Arterioscler Thromb Vasc Biol 25(1): 174-9
    › Primary publication · 15499039 (PubMed) · PMC2649706 (PubMed Central)
  40. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Boord JB, Maeda K, Makowski L, Babaev VR, Fazio S, Linton MF, Hotamisligil GS (2004) Circulation 110(11): 1492-8
    › Primary publication · 15353487 (PubMed) · PMC4027050 (PubMed Central)
  41. Unique pathway for cholesterol uptake in fat cells. Fazio S, Linton MF (2004) Arterioscler Thromb Vasc Biol 24(9): 1538-9
    › Primary publication · 15345518 (PubMed)
  42. Proatherogenic role for NK cells revealed. Linton MF, Major AS, Fazio S (2004) Arterioscler Thromb Vasc Biol 24(6): 992-4
    › Primary publication · 15178571 (PubMed)
  43. Hepatocyte-derived ApoE is more effective than non-hepatocyte-derived ApoE in remnant lipoprotein clearance. Raffaï RL, Hasty AH, Wang Y, Mettler SE, Sanan DA, Linton MF, Fazio S, Weisgraber KH (2003) J Biol Chem 278(13): 11670-5
    › Primary publication · 12551940 (PubMed)
  44. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MF (2001) Nat Med 7(6): 699-705
    › Primary publication · 11385507 (PubMed) · PMC4027052 (PubMed Central)
  45. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1. Accad M, Smith SJ, Newland DL, Sanan DA, King LE, Linton MF, Fazio S, Farese RV (2000) J Clin Invest 105(6): 711-9
    › Primary publication · 10727439 (PubMed) · PMC377465 (PubMed Central)
  46. Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. Cyrus T, Witztum JL, Rader DJ, Tangirala R, Fazio S, Linton MF, Funk CD (1999) J Clin Invest 103(11): 1597-604
    › Primary publication · 10359569 (PubMed) · PMC408369 (PubMed Central)
  47. On the relationship between cholesterol lowering and coronary disease event rate. Fazio S, Linton MF (1998) Circulation 98(23): 2645-6
    › Primary publication · 9843480 (PubMed)
  48. Long runs of adenines and human mutations. Raabe M, Linton MF, Young SG (1998) Am J Med Genet 76(1): 101-2
    › Primary publication · 9508075 (PubMed)
  49. Secretion from cell culture of HDL and VLDL bearing apoB-33 with a large internal deletion. Wu MJ, Chen-Liu LW, Xiao Q, Phillips ML, Elovson J, Linton MF, Young SG, Schumaker VN (1997) J Lipid Res 38(12): 2473-82
    › Primary publication · 9458271 (PubMed)
  50. Identification and characterization of truncated forms of apolipoprotein B in hypobetalipoproteinemia. Young SG, Krul ES, McCormick S, Farese RV, Linton MF (1996) Methods Enzymol : 120-45
    › Primary publication · 8749004 (PubMed)
  51. Familial hypobetalipoproteinemia. Linton MF, Farese RV, Young SG (1993) J Lipid Res 34(4): 521-41
    › Primary publication · 8496659 (PubMed)
  52. Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length. Young SG, Pullinger CR, Zysow BR, Hofmann-Radvani H, Linton MF, Farese RV, Terdiman JF, Snyder SM, Grundy SM, Vega GL (1993) J Lipid Res 34(3): 501-7
    › Primary publication · 8468533 (PubMed)
  53. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). Linton MF, Farese RV, Chiesa G, Grass DS, Chin P, Hammer RE, Hobbs HH, Young SG (1993) J Clin Invest 92(6): 3029-37
    › Primary publication · 8254057 (PubMed) · PMC288508 (PubMed Central)
  54. Transgenic mice expressing human apoB100 and apoB48. Young SG, Farese RV, Pierotti VR, Taylor S, Grass DS, Linton MF (1994) Curr Opin Lipidol 5(2): 94-101
    › Primary publication · 8044422 (PubMed)
  55. Expression of human apolipoprotein B90 in transgenic mice. Demonstration that apolipoprotein B90 lacks the structural requirements to form lipoprotein. McCormick SP, Linton MF, Hobbs HH, Taylor S, Curtiss LK, Young SG (1994) J Biol Chem 269(39): 24284-9
    › Primary publication · 7929084 (PubMed)
  56. Transgenic mice expressing high levels of human apolipoprotein B develop severe atherosclerotic lesions in response to a high-fat diet. Purcell-Huynh DA, Farese RV, Johnson DF, Flynn LM, Pierotti V, Newland DL, Linton MF, Sanan DA, Young SG (1995) J Clin Invest 95(5): 2246-57
    › Primary publication · 7738190 (PubMed) · PMC295837 (PubMed Central)
  57. Expression of P1 DNA in mammalian cells and transgenic mice. McCormick SP, Linton MF, Young SG (1994) Genet Anal Tech Appl 11(5-6): 158-64
    › Primary publication · 7710781 (PubMed)
  58. Comparison of the use of reserpine versus alpha-methyldopa for second step treatment of hypertension in the elderly. Applegate WB, Carper ER, Kahn SE, Westbrook L, Linton M, Baker MG, Runyan JW (1985) J Am Geriatr Soc 33(2): 109-15
    › Primary publication · 3968365 (PubMed)
  59. Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation. Linton MF, Gish R, Hubl ST, Bütler E, Esquivel C, Bry WI, Boyles JK, Wardell MR, Young SG (1991) J Clin Invest 88(1): 270-81
    › Primary publication · 2056122 (PubMed) · PMC296029 (PubMed Central)
  60. Expression of carboxyl-terminally truncated forms of human apolipoprotein B in rat hepatoma cells. Evidence that the length of apolipoprotein B has a major effect on the buoyant density of the secreted lipoproteins. Yao ZM, Blackhart BD, Linton MF, Taylor SM, Young SG, McCarthy BJ (1991) J Biol Chem 266(5): 3300-8
    › Primary publication · 1993701 (PubMed)
  61. Apolipoprotein B gene mutations affecting cholesterol levels. Farese RV, Linton MF, Young SG (1992) J Intern Med 231(6): 643-52
    › Primary publication · 1619387 (PubMed)
  62. Reading-frame restoration with an apolipoprotein B gene frameshift mutation. Linton MF, Pierotti V, Young SG (1992) Proc Natl Acad Sci U S A 89(23): 11431-5
    › Primary publication · 1454832 (PubMed) · PMC50565 (PubMed Central)