Pathology & Laboratory Medicine

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Center for Vascular Biology

Dr. Di Lorenzo’s laboratory is interested in two major area of research: one is to define the molecular mechanisms by which endothelial nitric oxide synthase (eNOS)-derived NO controls the endothelial barrier functions to the passage of plasma molecules and inflammatory cells.Another area of research focuses on the role of Nogo-B, belonging to the Reticulon-4 family of proteins expressed in the ER, in vascular function regulation and in cardiac hypertrophy development.

Active Projects

  • To study the role of eNOS in vascular permeability and inflammatory cell recruitment to the site of inflammation.
  • To investigate the role of Nogo-B in vascular function and cardiac hypertrophy.

Active Grants

  • Endothelial sphingolipid synthesis and tissue inflammatory response
    PI: Dr. Annarita Di Lorenzo, PhD
    National Institutes of Health (NIH)
  • Endothelial-derived Sphingolipids in Coronary Atherosclerosis
    PI: Annarita Di Lorenzo, PhD
    Harold S. Geneen Charitable Trust Awards Program for Coronary Heart Disease Research
  • Role of Nitric Oxide (NO) in Regulating VE-Cadherin Biological Functions
    PI: Annarita Di Lorenzo, PhD
    American Heart Association (AHA)

Selected Publications

Sphingolipids: Fats That Protect The Heart

Annarita Di Lorenzo, PhD

Sphingolipids: Fats That Protect The Heart

Scientia. Sep 13, 2017
Di Lorenzo A.
http://www.scientia.global/dr-annarita-di-lorenzo-sphingolipids-fats-protect-heart/

SciPod. October 2017
Di Lorenzo A.
http://www.scipod.global/sphingolipids-fats-that-protect-the-heart-dr-annarita-di-lorenzo-cornell-university/

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Estrogen Protects against Obesity-Induced Mammary Gland Inflammation in Mice

Domenick J. Falcone, PhD

Estrogen Protects against Obesity-Induced Mammary Gland Inflammation in Mice

Cancer Prev Res (Phila). 2015 Aug;8(8):751-9.

Bhardwaj P, Du B, Zhou XK, Sue E, Giri D, Harbus MD, Falcone DJ, Hudis CA, Subbaramaiah K, Dannenberg AJ.

PMID: 26038116; PMCID: PMC4526346

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Menopause is a determinant of breast adipose inflammation

Domenick J. Falcone, PhD

Menopause is a determinant of breast adipose inflammation

Cancer Prev Res (Phila). 2015 May;8(5):349-58.

Iyengar NM, Morris PG, Zhou XK, Gucalp A, Giri D, Harbus MD, Falcone DJ, Krasne MD, Vahdat LT, Subbaramaiah K, Morrow M, Hudis CA, Dannenberg AJ.

PMID: 25720743; PMCID: PMC4417434

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HIF-1α in vascular smooth muscle regulates blood pressure homeostasis through a PPARγ-angiotensin I receptor type 1 axis

Annarita Di Lorenzo, PhD

HIF-1α in vascular smooth muscle regulates blood pressure homeostasis through a PPARγ-angiotensin I receptor type 1 axis

Hypertension. 2013 Sep;62(3):634-40.

Huang Y, Di Lorenzo A, Jiang W, Cantalupo A, Sessa WC, Giordano FJ.

PMID: 23918749

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Caloric restriction reverses obesity-induced mammary gland inflammation in mice.

Domenick J. Falcone, PhD

Caloric restriction reverses obesity-induced mammary gland inflammation in mice.

Cancer Prev Res (Phila). 2013 Apr;6(4):282-9. 

Bhardwaj P, Du B, Zhou XK, Sue E, Harbus MD, Falcone DJ, Giri D, Hudis CA, Kopelovich L, Subbaramaiah K, Dannenberg AJ.

PMID: 23430756

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Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of vascular endothelial growth factor-A expression and angiogenesis.

Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of vascular endothelial growth factor-A expression and angiogenesis.

J Biol Chem. 2013 Feb 15;288(7):4908-21. 

Chang SH, Lu YC, Li X, Hsieh WY, Xiong Y, Ghosh M, Evans T, Elemento O, Hla T.

PMID: 23223443; PMCID: PMC3576095

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Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning.

Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning.

J Biol Chem. 2013 Jan 25;288(4):2143-56. 

Mendelson K, Zygmunt T, Torres-Vázquez J, Evans T, Hla T.

PMID: 23229546

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The annexin A2/S100A10 system in health and disease: emerging paradigms.

Domenick J. Falcone, PhD

The annexin A2/S100A10 system in health and disease: emerging paradigms.

J Biomed Biotechnol. 2012;2012:406273.

Hedhli N, Falcone DJ, Huang B, Cesarman-Maus G, Kraemer R, Zhai H, Tsirka SE, Santambrogio L, Hajjar KA.

PMID: 23193360

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Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development.

Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development.

Dev Cell. 2012 Sep 11;23(3):600-10. 

Jung B, Obinata H, Galvani S, Mendelson K, Ding BS, Skoura A, Kinzel B, Brinkmann V, Rafii S, Evans T, Hla T.

PMID: 22975328; PMCID: PMC3443394

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Matrix metalloproteinase (MMP)-dependent microsomal prostaglandin E synthase (mPGES)-1 expression in macrophages: Role of TNF-α and the EP4 prostanoid receptor

Domenick J. Falcone, PhD

Matrix metalloproteinase (MMP)-dependent microsomal prostaglandin E synthase (mPGES)-1 expression in macrophages: Role of TNF-α and the EP4 prostanoid receptor

J Immunol. 2012 Feb 15;188(4):1970-80.

Khan KM, Kothari P, Du B, Dannenberg AJ, Falcone DJ.

PMID: 22227567

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SnapShot: Bioactive lysophospholipids.

SnapShot: Bioactive lysophospholipids.

Cell. 2012 Jan 20;148(1-2):378-378.e2.

Moolenaar WH, Hla T.

PMID: 22265422

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ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation

Domenick J. Falcone, PhD

ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation

J Exp Med. 2012 Nov 19;209(12):2291-305.

Siao CJ, Lorentz CU, Kermani P, Marinic T, Carter J, McGrath K, Padow VA, Mark W, Falcone DJ, Cohen-Gould L, Parrish DC, Habecker BA, Nykjaer A, Ellenson LH, Tessarollo L, Hempstead BL.

PMID: 23091165; PMCID: PMC3501352

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Normal glucose uptake in the brain and heart requires an endothelial cell-specific HIF-1α-dependent function

Annarita Di Lorenzo, PhD

Normal glucose uptake in the brain and heart requires an endothelial cell-specific HIF-1α-dependent function

Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17478-83.

Huang Y, Lei L, Liu D, Jovin I, Russell R, Johnson RS, Di Lorenzo A, Giordano FJ.

PMID: 23047702; PMCID: PMC3491491

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Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer

Domenick J. Falcone, PhD

Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer

Cancer Prev Res (Phila). 2011 Jul;4(7):1021-9.

Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK, Du B, Brogi E, Crawford CB, Kopelovich L, Subbaramaiah K, Dannenberg AJ.

PMID: 21622727; PMCID: PMC3131426

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Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9613-8.

Christoffersen C, Obinata H, Kumaraswamy SB, Galvani S, Ahnström J, Sevvana M, Egerer-Sieber C, Muller YA, Hla T, Nielsen LB, Dahlbäck B.

PMID: 21606363; PMCID: PMC3111292

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Engagement of S1P₁-degradative mechanisms leads to vascular leak in mice

Engagement of S1P₁-degradative mechanisms leads to vascular leak in mice

J Clin Invest. 2011 Jun;121(6):2290-300. 

Oo MLChang SHThangada SWu MTRezaul KBlaho VHwang SIHan DKHla T.

PMID: 21555855

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Macrophages induce COX-2 expression in breast cancer cells: role of IL-1β autoamplification.

Domenick J. Falcone, PhD

Macrophages induce COX-2 expression in breast cancer cells: role of IL-1β autoamplification.

Carcinogenesis. 2011 May;32(5):695-702.

Hou Z, Falcone DJ, Subbaramaiah K, Dannenberg AJ.

PMID: 21310944

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Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.

Annarita Di Lorenzo, PhD

Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.

PLoS One. 2011 Apr 22;6(4):e18869. 

Albinsson S, Skoura A, Yu J, DiLorenzo A, Fernández-Hernando C, Offermanns S, Miano JM, Sessa WC.

PMID: 21526127

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Endothelial Reticulon-4B (Nogo-B) regulates ICAM-1-mediated leukocyte transmigration and acute inflammation

Annarita Di Lorenzo, PhD

Endothelial Reticulon-4B (Nogo-B) regulates ICAM-1-mediated leukocyte transmigration and acute inflammation

Blood. 2011 Feb 17;117(7):2284-95.

Di Lorenzo A, Manes TD, Davalos A, Wright PL, Sessa WC.

PMID: 21183689; PMCID: PMC3062334

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Sphingosine-1-phosphate receptor-2 function in myeloid cells regulates vascular inflammation and atherosclerosis

Sphingosine-1-phosphate receptor-2 function in myeloid cells regulates vascular inflammation and atherosclerosis

Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):81-5.

Skoura A, Michaud J, Im DS, Thangada S, Xiong Y, Smith JD, Hla T.

PMID: 20947824; PMCID: PMC3013369

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Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics

Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics

J Exp Med. 2010 Jul 5;207(7):1475-83.

Thangada S, Khanna KM, Blaho VA, Oo ML, Im DS, Guo C, Lefrancois L, Hla T.

PMID: 20584883; PMCID: PMC2901064

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Sin1-mTORC2 suppresses rag and il7r gene expression through Akt2 in B cells

Annarita Di Lorenzo, PhD

Sin1-mTORC2 suppresses rag and il7r gene expression through Akt2 in B cells

Mol Cell. 2010 Aug 13;39(3):433-43.

Lazorchak AS, Liu D, Facchinetti V, Di Lorenzo A, Sessa WC, Schatz DG, Su B.

PMID: 20705244; PMCID: PMC2957800

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Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice

Annarita Di Lorenzo, PhD

Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice

Lab Invest. 2010 Nov;90(11):1573-81.

Krieger MH, Di Lorenzo A, Teutsch C, Kauser K, Sessa WC.

PMID: 20585312; PMCID: PMC3248785

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CCM3 signaling through sterile 20-like kinases plays an essential role during zebrafish cardiovascular development and cerebral cavernous malformations

Annarita Di Lorenzo, PhD

CCM3 signaling through sterile 20-like kinases plays an essential role during zebrafish cardiovascular development and cerebral cavernous malformations

J Clin Invest. 2010 Aug;120(8):2795-804.

Zheng X, Xu C, Di Lorenzo A, Kleaveland B, Zou Z, Seiler C, Chen M, Cheng L, Xiao J, He J, Pack MA, Sessa WC, Kahn ML.

PMID: 20592472; PMCID: PMC2912181

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Matrix metalloproteinase (MMP)-1 and MMP-3 induce macrophage MMP-9: Evidence for the role of TNF-∝ and cyclooxygenase-2.

Domenick J. Falcone, PhD

Matrix metalloproteinase (MMP)-1 and MMP-3 induce macrophage MMP-9: Evidence for the role of TNF-∝ and cyclooxygenase-2.

J Immunol. 2009 Dec 15;183(12):8119-27.

Steenport M, Khan KM, Du B, Barnhard SE, Dannenberg AJ, Falcone DJ.

PMID: 19923455; PMCID: PMC3621723

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Essential role of the RNA-binding protein HuR in progenitor cell survival in mice

Essential role of the RNA-binding protein HuR in progenitor cell survival in mice

J Clin Invest. 2009 Dec;119(12):3530-43.

Ghosh M, Aguila HL, Michaud J, Ai Y, Wu MT, Hemmes A, Ristimaki A, Guo C, Furneaux H, Hla T.

PMID: 19884656; PMCID: PMC2786787

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Hydrogen sulphide is involved in testosterone vascular effect

Annarita Di Lorenzo, PhD

Hydrogen sulphide is involved in testosterone vascular effect

Eur Urol. 2009 Aug;56(2):378-83.

Bucci M, Mirone V, Di Lorenzo A, Vellecco V, Roviezzo F, Brancaleone V, Ciro I, Cirino G.

PMID: 18511180

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Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair

Annarita Di Lorenzo, PhD

Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair

Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17511-6.

Yu J, Fernández-Hernando C, Suarez Y, Schleicher M, Hao Z, Wright PL, DiLorenzo A, Kyriakides TR, Sessa WC.

PMID: 19805174; PMCID: PMC2762666

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Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis

Annarita Di Lorenzo, PhD

Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis

Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2033-40.

Fernández-Hernando C, József L, Jenkins D, Di Lorenzo A, Sessa WC.

PMID: 19762778; PMCID: PMC2796372

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Akt1 is critical for acute inflammation and histamine-mediated vascular leakage

Annarita Di Lorenzo, PhD

Akt1 is critical for acute inflammation and histamine-mediated vascular leakage

Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14552-7.

Di Lorenzo A, Fernández-Hernando C, Cirino G, Sessa WC.

PMID: 19622728; PMCID: PMC2732859

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The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo

Annarita Di Lorenzo, PhD

The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo

Sci Signal. 2009 Aug 4;2(82):ra41.

Schleicher M, Yu J, Murata T, Derakhshan B, Atochin D, Qian L, Kashiwagi S, Di Lorenzo A, Harrison KD, Huang PL, Sessa WC.

PMID: 19654415

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Vascular endothelium as a contributor of plasma sphingosine 1-phosphate

Vascular endothelium as a contributor of plasma sphingosine 1-phosphate

Circ Res. 2008 Mar 28;102(6):669-76.

Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y, Bonkovsky HL, Parikh NS, Habrukowich C, Hla T.

PMID: 18258856; PMCID: PMC2659392

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Tobacco smoke induces urokinase-type plasminogen activator and cell invasiveness: Evidence for an EGFR-dependent mechanism

Domenick J. Falcone, PhD

Tobacco smoke induces urokinase-type plasminogen activator and cell invasiveness: Evidence for an EGFR-dependent mechanism

Cancer Res. 2007 Sep 15;67(18):8966-72.

Du B, Leung H, Khan KM, Miller CG, Subbaramaiah K, Falcone DJ, Dannenberg AJ.

PMID: 17875740

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Sphingosine-1-phosphate/sphingosine kinase pathway is involved in mouse airway hyperresponsiveness

Annarita Di Lorenzo, PhD

Sphingosine-1-phosphate/sphingosine kinase pathway is involved in mouse airway hyperresponsiveness

Am J Respir Cell Mol Biol. 2007 Jun;36(6):757-62. 

Roviezzo F, Di Lorenzo A, Bucci M, Brancaleone V, Vellecco V, De Nardo M, Orlotti D, De Palma R, Rossi F, D'Agostino B, Cirino G.

PMID: 17322125.

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Targeting PGE2 receptors as an alternative strategy to block COX-2-dependent extracellular matrix-induced MMP-9 expression by macrophages

Domenick J. Falcone, PhD

Targeting PGE2 receptors as an alternative strategy to block COX-2-dependent extracellular matrix-induced MMP-9 expression by macrophages

J Biol Chem. 2006 Feb 10;281(6):3321-8. 

Pavlovic S, Du B, Sakamoto K, Khan KM, Natarajan C, Breyer RM, Dannenberg AJ, Falcone DJ. 

PMID: 16338931

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Extracellular matrix induced cyclooxygenase-2 regulates macrophage proteinase expression

Domenick J. Falcone, PhD

Extracellular matrix induced cyclooxygenase-2 regulates macrophage proteinase expression

J Biol Chem. 2004 May 21;279(21):22039-46. 

Khan KM, Howe LR, Falcone DJ.

PMID: 15024003

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Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: Enhanced expression by macrophages

Domenick J. Falcone, PhD

Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: Enhanced expression by macrophages

Blood. 2004 Jan 1;103(1):317-24.

Brownstein C, Deora AB, Jacovina AT, Weintraub R, Gertler M, Khan KM, Falcone DJ, Hajjar KA.

PMID: 14504107

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Exposure of cryptic domains in the alpha1-chain of laminin-1 by elastase stimulates macrophages urokinase and MMP-9 expression

Domenick J. Falcone, PhD

Exposure of cryptic domains in the alpha1-chain of laminin-1 by elastase stimulates macrophages urokinase and MMP-9 expression

J Biol Chem. 2002 Apr 19;277(16):13778-86.

Faisal Khan KM, Laurie GW, McCaffrey TA, Falcone DJ.

PMID: 11827968

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Myocardial fibrosis in chronic aortic regurgitation: molecular and cellular responses to volume overload

Domenick J. Falcone, PhD

Myocardial fibrosis in chronic aortic regurgitation: molecular and cellular responses to volume overload

Circulation. 2002 Apr 16;105(15):1837-42.

Borer JS, Truter S, Herrold EM, Falcone DJ, Pena M, Carter JN, Dumlao TF, Lee JA, Supino PG. 

PMID: 11956128

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Nerve growth factor activation of erk-1 and erk-2 induces matrix metalloproteinase expression in vascular smooth muscle cells.

Domenick J. Falcone, PhD

Nerve growth factor activation of erk-1 and erk-2 induces matrix metalloproteinase expression in vascular smooth muscle cells.

J Biol Chem. 2002 Jan 18;277(3):2353-9.

Khan KM, Falcone DJ, Kraemer

PMID: 11698409

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Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II

Domenick J. Falcone, PhD

Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II

Blood. 2001 Feb 1;97(3):777-84. 

Falcone DJ, Borth W, Khan KM, Hajjar KA.

PMID: 11157497

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Selective activation of MAPKerk1/2 by laminin-1 peptide alpha1:Ser2091-Arg2108 regulates macrophage degradative phenotype

Domenick J. Falcone, PhD

Selective activation of MAPKerk1/2 by laminin-1 peptide alpha1:Ser2091-Arg2108 regulates macrophage degradative phenotype

J Biol Chem. 2000 Feb 11;275(6):4492-8.

Khan KM, Falcone DJ.

PMID: 10660623

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Macrophage formation of angiostatin during inflammation: A byproduct of the activation of plasminogen. J

Domenick J. Falcone, PhD

Macrophage formation of angiostatin during inflammation: A byproduct of the activation of plasminogen. J

J Biol Chem. 1998 Nov 20;273(47):31480-5.

Falcone DJ, Khan KM, Layne T, Fernandes L.

PMID: 9813061

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