Biomedical Research Education & Training
Faculty Member

Fazio, Sergio, M.D., Ph.D.
Professor of Medicine
Cornelius Vanderbilt Chair
Professor of Pathology, Microbiology and Immunology

Lab Url: N/A

Phone Number: 615-936-1651

Email Address:

Fazio, Sergio's picture
Academic history
M.D., University of Rome, Rome, Italy
Ph.D., University of Siena, Siena, Italy
N/A, University of California, San Francisco

Office Address   Mailing Address

383 PRB 2220 Pierce Avenue

383 PRB 6300

Research Keywords
Dyslipidemias, Atherosclerosis, Coronary disease, Mouse models, Macrophages, Vascular Biology, Apolipoproteins, Knockout Mouse, Stem cells,Transplantation

Research Specialty
Macrophage-based gene therapy of hypercholesterolemia and atherosclerosis

Research Description
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. .

Fazio, S, Linton, MF. Proprotein convertase subtilisin/kexin type 9 as transducer of physiologic influences on cellular cholesterol: a case for resistin. J Am Coll Cardiol, 59(19), 1706-8, 2012

Fazio, S, Linton, MF. Inhibition of apolipoprotein(a) synthesis by farnesoid X receptor and fibroblast growth factor 15/19: a step toward selective lipoprotein(a) therapeutics. Arterioscler Thromb Vasc Biol, 32(5), 1060-2, 2012

Lilley, JS, Linton, MF, Fazio, S. Dyslipidemias in children. Pediatr Ann, 41(2), e1-7, 2012

Martinez, MN, Emfinger, CH, Overton, M, Hill, S, Ramaswamy, TS, Cappel, DA, Wu, K, Fazio, S, McDonald, WH, Hachey, DL, Tabb, DL, Stafford, JM. Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones. J Lipid Res, 53(3), 379-89, 2012 PMCID:3312235

Minicocci, I, Montali, A, Robciuc, MR, Quagliarini, F, Censi, V, Labbadia, G, Gabiati, C, Pigna, G, Sepe, ML, Pannozzo, F, L??tjohann, D, Fazio, S, Jauhiainen, M, Ehnholm, C, Arca, M. Mutations in the ANGPTL3 Gene and Familial Combined Hypolipidemia: A Clinical and Biochemical Characterization. J Clin Endocrinol Metab, 97(7), E1266-75, 2012

Prins, PA, Perati, PR, Kon, V, Guo, Z, Ramesh, A, Linton, MF, Fazio, S, Sampson, UK. Benzo[a]pyrene potentiates the pathogenesis of abdominal aortic aneurysms in apolipoprotein E knockout mice. Cell Physiol Biochem, 29(1-2), 121-30, 2012

Sampson, UK, Fazio, S, Linton, MF. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep, 14(1), 1-10, 2012

Villegas, R, Xiang, YB, Elasy, T, Xu, WH, Cai, H, Cai, Q, Linton, MF, Fazio, S, Zheng, W, Shu, XO. Purine-rich foods, protein intake, and the prevalence of hyperuricemia: the Shanghai men''s health study. Nutr Metab Cardiovasc Dis, 22(5), 409-16, 2012 PMCID:3094053

Babaev, VR, Runner, RP, Fan, D, Ding, L, Zhang, Y, Tao, H, Erbay, E, G??rg??n, CZ, Fazio, S, Hotamisligil, GS, Linton, MF. Macrophage Mal1 deficiency suppresses atherosclerosis in low-density lipoprotein receptor-null mice by activating peroxisome proliferator-activated receptor-I?-regulated genes. Arterioscler Thromb Vasc Biol, 31(6), 1283-90, 2011 PMCID:3135083

Du, F, Hui, Y, Zhang, M, Linton, MF, Fazio, S, Fan, D. Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem, 286(50), 43054-61, 2011

Fazio, S, Linton, MF. Low levels of high-density lipoprotein cholesterol due to lecithin:cholesterol acyltransferase mutations increase carotid atherosclerosis. J Am Coll Cardiol, 58(24), 2488-90, 2011

Kon, V, Linton, MF, Fazio, S. Atherosclerosis in chronic kidney disease: the role of macrophages. Nat Rev Nephrol, 7(1), 45-54, 2011 PMCID:3203394

Levin, MC, Lidberg, U, Jirholt, P, Adiels, M, Wramstedt, A, Gustafsson, K, Greaves, DR, Li, S, Fazio, S, Linton, MF, Olofsson, SO, Bor??n, J, Gjertsson, I. Evaluation of macrophage-specific promoters using lentiviral delivery in mice. Gene Ther, 2011

Ma, LJ, Corsa, BA, Zhou, J, Yang, H, Li, H, Tang, YW, Babaev, VR, Major, AS, Linton, MF, Fazio, S, Hunley, TE, Kon, V, Fogo, AB. Angiotensin type 1 receptor modulates macrophage polarization and renal injury in obesity. Am J Physiol Renal Physiol, 300(5), F1203-13, 2011 PMCID:3094053

Ormseth, MJ, Swift, LL, Fazio, S, Linton, MF, Chung, CP, Raggi, P, Rho, YH, Solus, J, Oeser, A, Bian, A, Gebretsadik, T, Shintani, A, Stein, CM. Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis. Atherosclerosis, 219(2), 869-74, 2011

Rana, T, Misra, S, Mittal, MK, Farrow, AL, Wilson, KT, Linton, MF, Fazio, S, Willis, IM, Chaudhuri, G. Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania. J Biol Chem, 286(8), 6614-26, 2011 PMCID:3057815

Rosenson, RS, Brewer, HB, Chapman, MJ, Fazio, S, Hussain, MM, Kontush, A, Krauss, RM, Otvos, JD, Remaley, AT, Schaefer, EJ. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem, 57(3), 392-410, 2011 PMCID:3094053

Sampson, UK, Linton, MF, Fazio, S. Are statins diabetogenic. Curr Opin Cardiol, 26(4), 342-7, 2011 PMCID:3341610

Sampson, UK, Perati, PR, Prins, PA, Pham, W, Liu, Z, Harrell, FE, Linton, MF, Gore, JC, Kon, V, Fazio, S. Quantitative estimates of the variability of in vivo sonographic measurements of the mouse aorta for studies of abdominal aortic aneurysms and related arterial diseases. J Ultrasound Med, 30(6), 773-84, 2011 PMCID:3144781

Villegas, R, Xiang, YB, Elasy, T, Cai, Q, Xu, W, Li, H, Fazio, S, Linton, MF, Raiford, D, Zheng, W, Shu, XO. Liver enzymes, type 2 diabetes, and metabolic syndrome in middle-aged, urban Chinese men. Metab Syndr Relat Disord, 9(4), 305-11, 2011 PMCID:3142636

Woo, KV, Qu, X, Babaev, VR, Linton, MF, Guzman, RJ, Fazio, S, Baldwin, HS. Tie1 attenuation reduces murine atherosclerosis in a dose-dependent and shear stress-specific manner. J Clin Invest, 121(4), 1624-35, 2011 PMCID:3069759

Yamamoto, S, Yancey, PG, Zuo, Y, Ma, LJ, Kaseda, R, Fogo, AB, Ichikawa, I, Linton, MF, Fazio, S, Kon, V. Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis. Arterioscler Thromb Vasc Biol, 31(12), 2856-64, 2011

Yamamoto, S, Zuo, Y, Ma, J, Yancey, PG, Hunley, TE, Motojima, M, Fogo, AB, Linton, MF, Fazio, S, Ichikawa, I, Kon, V. Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice. Nephrol Dial Transplant, 26(8), 2491-7, 2011 PMCID:3203394

Yancey, PG, Ding, Y, Fan, D, Blakemore, JL, Zhang, Y, Ding, L, Zhang, J, Linton, MF, Fazio, S. 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. Circulation, 124(4), 454-64, 2011 PMCID:3144781

Affuso, F, Ruvolo, A, Micillo, F, Sacc? , L, Fazio, S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis, 20(9), 656-61, 2010 PMCID:2924448

Babaev, VR, Li, L, Shah, S, Fazio, S, Linton, MF, May, JM. Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol, 30(9), 1751-7, 2010 PMCID:2924448

Fazio, S, Guyton, JR, Lin, J, Tomassini, JE, Shah, A, Tershakovec, AM. Long-term efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in hyperlipidaemic patients with diabetes or metabolic syndrome. Diabetes Obes Metab, 12(11), 983-93, 2010 PMCID:3203394

Fazio, S, Guyton, JR, Polis, AB, Adewale, AJ, Tomassini, JE, Ryan, NW, Tershakovec, AM. Long-term safety and efficacy of triple combination ezetimibe/simvastatin plus extended-release niacin in patients with hyperlipidemia. Am J Cardiol, 105(4), 487-94, 2010 PMCID:2924448

Fazio, S, Linton, MF. High-density lipoprotein therapeutics and cardiovascular prevention. J Clin Lipidol, 4(5), 411-9, 2010 PMCID:3203394

Lewis, TL, Cao, D, Lu, H, Mans, RA, Su, YR, Jungbauer, L, Linton, MF, Fazio, S, LaDu, MJ, Li, L. Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease. J Biol Chem, 285(47), 36958-68, 2010 PMCID:2978624

Houston, MC, Fazio, S, Chilton, FH, Wise, DE, Jones, KB, Barringer, TA, Bramlet, DA. Nonpharmacologic treatment of dyslipidemia. Prog Cardiovasc Dis, 52(2), 61-94, 2009 PMCID:2924448

Zuo, Y, Yancey, P, Castro, I, Khan, WN, Khan, W, Motojima, M, Ichikawa, I, Fogo, AB, Linton, MF, Fazio, S, Kon, V. Renal dysfunction potentiates foam cell formation by repressing ABCA1. Arterioscler Thromb Vasc Biol, 29(9), 1277-82, 2009 PMCID:2748735

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