Our main research interest is the pathogenesis of plasma lipoprotein alterations and the mechanisms of early atherogensis. Early atherosclerotic lesions are characterized by recruitment of macrophages. We are focusing on the macrophage as a cell with a potential role in both lipoprotein metabolism and atherogenesis. The macrophage plays an important role in the regulation of lipoprotein metabolism and in the process of atherogenesis. It produces proteins (such as lipoprotein receptors, apoE, and lipoprotein lipase) that can control the levels of plasma cholesterol and triglycerides, and it represents a common cell type of the atherosclerotic lesion, where it eventually transforms into a foam cell, a typical finding in the early plaque. Since tissue macrophages derive from circulating monocytes, we are currently using bone marrow transplantation as a way to study the contribution of normal or genetically engineered macrophages to the regulation of lipoprotein metabolism and to the development of atherosclerosis in the mouse. We are following several areas of investigation: 1. Study the role that macrophage apoE production plays in the induction, progression, and regression of the atherosclerotic process. 2. Study the effects of over-expression of apoE by the macrophage on cholesterol levels and atherosclerosis susceptibility in mouse models of hypercholesterolemia other than apoE deficiency. 3. Dissect the role played in vivo by macrophage lipoprotein receptors (LDL receptor, scavenger receptor, and the remnant receptor) in determining progression to foam cell. 4. Analyze the use of macrophage as vehicles of proteins not normally expressed by this cell type, such as apoAI, to delay atherosclerosis. These studies have the potential to clarify the role of macrophage apoE in the control of lipoprotein metabolism and in the process of atherogenesis and will set the stage for a novel gene therapy approach to hypercholesterolemia and atherosclerosis. .


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

  1. Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization. Minicocci I, Montali A, Robciuc MR, Quagliarini F, Censi V, Labbadia G, Gabiati C, Pigna G, Sepe ML, Pannozzo F, Lütjohann D, Fazio S, Jauhiainen M, Ehnholm C, Arca M (2012) J Clin Endocrinol Metab 97(7): E1266-75
    › Primary publication · 22659251 (PubMed) · PMC5393441 (PubMed Central)
  2. Proprotein convertase subtilisin/kexin type 9 as transducer of physiologic influences on cellular cholesterol: a case for resistin. Fazio S, Linton MF (2012) J Am Coll Cardiol 59(19): 1706-8
    › Primary publication · 22554601 (PubMed)
  3. Inhibition of apolipoprotein(a) synthesis by farnesoid X receptor and fibroblast growth factor 15/19: a step toward selective lipoprotein(a) therapeutics. Fazio S, Linton MF (2012) Arterioscler Thromb Vasc Biol 32(5): 1060-2
    › Primary publication · 22517359 (PubMed)
  4. Benzo[a]pyrene potentiates the pathogenesis of abdominal aortic aneurysms in apolipoprotein E knockout mice. Prins PA, Perati PR, Kon V, Guo Z, Ramesh A, Linton MF, Fazio S, Sampson UK (2012) Cell Physiol Biochem 29(1-2): 121-30
    › Primary publication · 22415081 (PubMed) · PMC3711770 (PubMed Central)
  5. Dyslipidemias in children. Lilley JS, Linton MF, Fazio S (2012) Pediatr Ann 41(2): e1-7
    › Primary publication · 22299622 (PubMed)
  6. Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones. Martinez MN, Emfinger CH, Overton M, Hill S, Ramaswamy TS, Cappel DA, Wu K, Fazio S, McDonald WH, Hachey DL, Tabb DL, Stafford JM (2012) J Lipid Res 53(3): 379-389
    › Primary publication · 22215797 (PubMed) · PMC3276461 (PubMed Central)
  7. Low levels of high-density lipoprotein cholesterol due to lecithin:cholesterol acyltransferase mutations increase carotid atherosclerosis. Fazio S, Linton MF (2011) J Am Coll Cardiol 58(24): 2488-90
    › Primary publication · 22133848 (PubMed)
  8. Evaluation of macrophage-specific promoters using lentiviral delivery in mice. Levin MC, Lidberg U, Jirholt P, Adiels M, Wramstedt A, Gustafsson K, Greaves DR, Li S, Fazio S, Linton MF, Olofsson SO, Borén J, Gjertsson I (2012) Gene Ther 19(11): 1041-7
    › Primary publication · 22130447 (PubMed) · PMC3697098 (PubMed Central)
  9. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Sampson UK, Fazio S, Linton MF (2012) Curr Atheroscler Rep 14(1): 1-10
    › Primary publication · 22102062 (PubMed) · PMC3697085 (PubMed Central)
  10. Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. Du F, Hui Y, Zhang M, Linton MF, Fazio S, Fan D (2011) J Biol Chem 286(50): 43054-61
    › Primary publication · 22027821 (PubMed) · PMC3234880 (PubMed Central)