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Joseph Loscalzo, MD, PhD: A Conversation With the Editor*

    Published:February 14, 2006DOI:https://doi.org/10.1016/j.amjcard.2005.12.021
        Joseph Loscalzo is the Hersey Professor of the Theory and Practice of Medicine at Harvard Medical School, Chairman of the Department of Medicine and Physician-in-Chief at the Brigham and Women’s Hospital in Boston, Massachusetts, and also Vice Director of the Brigham Biomedical Research Institute. He was born in 1951 in Camden, New Jersey, and that is where he grew up. His precollege training was provided at Catholic schools. He completed college, medical school education, and graduate school at the University of Pennsylvania in Philadelphia. He graduated from college after 3 years in 1972, summa cum laude, and from medical school in December 1977, receiving both a PhD in biochemistry and an MD (officially conferred in May 1978). He trained as an intern and resident in internal medicine at the Brigham and Women’s Hospital, and following a fellowship in cardiology at the same hospital, he was appointed chief resident physician in internal medicine at the Brigham and Women’s Hospital, finishing in June 1984. He remained on the staff thereafter, rising to the rank of associate professor of medicine, Harvard Medical School, by 1989. In 1994, he moved to the Boston University School of Medicine, where he was appointed the Distinguished Professor of Cardiovascular Medicine, Professor of Biochemistry, and Director of the Whitaker Cardiovascular Institute. In 1997, he became the Wade Professor and Chairman of the Department of Medicine of Boston University School of Medicine. In July, 2005, he returned to the Brigham and Women’s Hospital to assume his present positions (Figure 1).
        Figure thumbnail gr1
        Figure 1JL sitting at his desk.
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        Best Publications as Chosen by JL (in order as they appear on his CV)

          • Loscalzo J.
          N-acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin.
          J Clin Invest. 1985; 76: 703-708
          • Loscalzo J.
          • Inbal A.
          • Handin R.I.
          von Willebrand protein facilitates platelet incorporation in polymerizing fibrin.
          J Clin Invest. 1986; 78: 1112-1119
          • Loscalzo J.
          • Slayter H.
          • Handin R.I.
          • Farber D.
          Subunit structure and assembly of von Willebrand factor polymer. Complementary analysis by electron microscopy and quasielastic light scattering.
          Biophy J. 1986; 49: 49-50
          • Loscalzo J.
          Paradoxical embolism.
          Am Heart J. 1986; 112: 141-145
          • Janicki J.S.
          • Weber K.T.
          • Loscalzo J.
          • Shroff S.
          Extracardiac pressure and ventricular haemodynamics.
          Cardiovasc Res. 1987; 21: 230-239
          • Loscalzo J.
          • Vaughan D.E.
          Tissue plasminogen activator promotes platelet disaggregation in plasma.
          J Clin Invest. 1987; 79: 1749-1755
          • Loscalzo J.
          Structural and kinetic comparison of recombinant human single- and two-chain tissue plasminogen activator.
          J Clin Invest. 1988; 82: 1391-1397
          • Loscalzo J.
          • Braunwald E.
          Tissue plasminogen activator.
          N Engl J Med. 1988; 319: 925-931
          • Mendelsohn M.E.
          • Loscalzo J.
          Role of platelets in cholesteryl ester formation by U-937 cells.
          J Clin Invest. 1988; 81: 62-68
          • Loscalzo J.
          • Smick D.
          • Andon N.
          • Cooke J.
          S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets.
          J Pharmacol Exp Ther. 1989; 249: 726-729
          • Stamler J.
          • Mendelsohn M.E.
          • Amarante P.
          • Smick D.
          • Andon N.
          • Davies P.F.
          • Cooke J.P.
          • Loscalzo J.
          N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.
          Circ Res. 1989; 65: 789-795
          • Vaughan D.E.
          • Mendelsohn M.E.
          • Declerck P.J.
          • Van Houtte E.
          • Collen D.
          • Loscalzo J.
          Characterization of the binding of human tissue-type plasminogen activator to platelets.
          J Biol Chem. 1989; 264: 15869-15874
          • Vaughan D.E.
          • Plavin S.R.
          • Schafer A.I.
          • Loscalzo J.
          PGE1 accelerates thrombolysis by tissue plasminogen activator.
          Blood. 1989; 73: 1213-1217
          • Cooke J.P.
          • Stamler J.
          • Andon N.
          • Davies P.F.
          • McKinley G.
          • Loscalzo J.
          Flow stimulates endothelial cells to release nitrovasodilator that is potentiated by reduced thiol.
          Am J Physiol. 1990; 259: H804-H812
          • Kuo P.
          • Weinfeld M.
          • Loscalzo J.
          Effect of membrane fatty acyl composition on LDL metabolism in Hep G2 hepatocytes.
          Biochemistry. 1990; 29: 6626-6632
          • Loscalzo J.
          • Weinfeld M.
          • Fless G.M.
          • Scanu A.M.
          Lipoprotein(a), fibrin binding, and plasminogen activation.
          Arteriosclerosis. 1990; 10: 240-245
          • Mendelsohn M.E.
          • O’Neill S.
          • George D.
          • Loscalzo J.
          Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine.
          J Biol Chem. 1990; 265: 19028-19034
          • Folts J.D.
          • Stamler J.
          • Loscalzo J.
          Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries.
          Circulation. 1991; 83: 2122-2127
          • Simon D.I.
          • Fless G.M.
          • Scanu A.M.
          • Loscalzo J.
          Tissue-type plasminogen activator binds to and is inhibited by surface-bound lipoprotein(a) and low-density lipoprotein.
          Biochemistry. 1991; 30: 6671-6677
          • Loscalzo J.
          Endothelial dysfunction in pulmonary hypertension.
          N Engl J Med. 1992; 327: 117-119
          • McIntyre K.M.
          • Vita J.A.
          • Lambrew C.T.
          • Freedman J.
          • Loscalzo J.
          A noninvasive method of predicting pulmonary-capillary wedge pressure.
          N Engl J Med. 1992; 327: 1715-1720
          • Rudd M.A.
          • George D.
          • Johnstone M.T.
          • Moore R.T.
          • Collins L.
          • Rabbani L.E.
          • Loscalzo J.
          Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy.
          Circ Res. 1992; 70: 829-834
          • Stamler J.S.
          • Singel D.J.
          • Loscalzo J.
          Biochemistry of nitric oxide and its redox-activated forms.
          Science. 1992; 258: 1898-1902
          • Stamler J.S.
          • Simon D.I.
          • Osborne J.A.
          • Mullins M.E.
          • Jaraki O.
          • Michel T.
          • Singel D.J.
          • Loscalzo J.
          S-nitrosylation of proteins with nitric oxide.
          Proc Natl Acad Sci USA. 1992; 89: 444-448
          • Stamler J.S.
          • Jaraki O.
          • Osborne J.
          • Simon D.I.
          • Keaney J.
          • Vita J.
          • Singel D.
          • Valeri C.R.
          • Loscalzo J.
          Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.
          Proc Natl Acad Sci USA. 1992; 89: 7674-7677
          • Keaney Jr, J.F.
          • Simon D.I.
          • Stamler J.S.
          • Jaraki O.
          • Scharfstein J.
          • Vita J.A.
          • Loscalzo J.
          NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties.
          J Clin Invest. 1993; 91: 1582-1589
          • Simon D.I.
          • Ezratty A.M.
          • Francis S.A.
          • Rennke H.
          • Loscalzo J.
          Fibrin(ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18).
          Blood. 1993; 82: 2414-2422
          • Pasche B.
          • Ouimet H.
          • Francis S.
          • Loscalzo J.
          Structural changes in platelet glycoprotein IIb/IIIa by plasmin.
          Blood. 1994; 83: 404-414
          • Scharfstein J.S.
          • Keaney Jr, J.F.
          • Slivka A.
          • Welch G.N.
          • Vita J.A.
          • Stamler J.S.
          • Loscalzo J.
          In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols.
          J Clin Invest. 1994; 94: 1432-1439
          • Simon D.I.
          • Ezratty A.M.
          • Loscalzo J.
          The fibrin(ogen)olytic properties of cathepsin D.
          Biochemistry. 1994; 33: 6555-6563
          • Freedman J.E.
          • Frei B.
          • Welch G.N.
          • Loscalzo J.
          Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols.
          J Clin Invest. 1995; 96: 394-400
          • Marks D.S.
          • Vita J.A.
          • Folts J.D.
          • Keaney Jr, J.F.
          • Welch G.N.
          • Loscalzo J.
          Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.
          J Clin Invest. 1995; 96: 2630-2638
          • Freedman J.E.
          • Loscalzo J.
          • Benoit S.E.
          • Valeri C.R.
          • Barnard M.R.
          • Michelson A.D.
          Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis.
          J Clin Invest. 1996; 97: 979-987
          • Michelson A.D.
          • Benoit S.E.
          • Furman M.I.
          • Breckwoldt W.L.
          • Rohrer M.J.
          • Barnard M.R.
          • Loscalzo J.
          Effects of nitric oxide/EDRF on platelet surface glycoproteins.
          Am J Physiol. 1996; 270: H1640-H1648
          • Freedman J.E.
          • Loscalzo J.
          • Barnard M.R.
          • Alpert C.
          • Keaney Jr, J.F.
          • Michelson A.D.
          Nitric oxide released from activated platelets inhibits platelet recruitment.
          J Clin Invest. 1997; 100: 350-356
          • Upchurch Jr, G.R.
          • Welch G.N.
          • Fabian A.J.
          • Freedman J.E.
          • Johnson J.L.
          • Keaney Jr, J.F.
          • Loscalzo J.
          Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase.
          J Biol Chem. 1997; 272: 17012-17017
          • Welch G.N.
          • Upchurch Jr, G.R.
          • Farivar R.S.
          • Pigazzi A.
          • Vu K.
          • Brecher P.
          • Keaney Jr, J.F.
          • Loscalzo J.
          Homocysteine-induced nitric oxide production in vascular smooth-muscle cells by NF-kappa B-dependent transcriptional activation of Nos2.
          Proc Assoc Am Physicians. 1998; 110: 22-31
          • Freedman J.E.
          • Sauter R.
          • Battinelli E.M.
          • Ault K.
          • Knowles C.
          • Huang P.L.
          • Loscalzo J.
          Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene.
          Circ Res. 1999; 84: 1416-1421
          • Kenet G.
          • Freedman J.
          • Shenkman B.
          • Regina E.
          • Brok-Simoni F.
          • Holzman F.
          • Vavva F.
          • Brand N.
          • Michelson A.
          • Trolliet M.
          • Loscalzo J.
          • Inbal A.
          Plasma glutathione peroxidase deficiency and platelet insensitivity to nitric oxide in children with familial stroke.
          Arterioscl Thromb Vasc Biol. 1999; 19: 2017-2023
          • Pigazzi A.
          • Heydrick S.
          • Folli F.
          • Benoit S.
          • Michelson A.
          • Loscalzo J.
          Nitric oxide inhibits thrombin-receptor-activating peptide-induced phosphoinositide 3-kinase activity in human platelets.
          J Biol Chem. 1999; 274: 14368-14375
          • Rudd M.A.
          • Trolliet M.
          • Hope S.
          • Scribner A.M.
          • Daumerie G.
          • Toolan G.
          • Cloutier T.
          • Loscalzo J.
          Salt-induced hypertension in Dahl salt-resistant and salt-sensitive rats with NOS II inhibition.
          Am J Physiol. 1999; 277: H732-H739
          • Zai A.
          • Rudd M.A.
          • Scribner A.W.
          • Loscalzo J.
          Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide.
          J Clin Invest. 1999; 103: 393-399
          • Battinelli E.M.
          • Loscalzo J.
          Nitric oxide induces apoptosis in megakaryocytic cell lines.
          Blood. 2000; 95: 3451-3459
          • Eberhardt R.T.
          • Forgione M.A.
          • Cap A.
          • Leopold J.A.
          • Rudd M.A.
          • Trolliet M.T.
          • Heydrick S.
          • Stark R.
          • Klings E.S.
          • Moldovan N.I.
          • Yaghoubi M.
          • Goldschmidt-Clermont P.J.
          • Farber H.W.
          • Cohen R.A.
          • Loscalzo J.
          Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia.
          J Clin Invest. 2000; 106: 483-491
          • Loscalzo J.
          Nitric oxide insufficiency, platelet activation, and arterial thrombosis.
          Circ Res. 2001; 88: 756-762
          • Leopold J.A.
          • Cap A.
          • Scribner A.W.
          • Stanton R.C.
          • Loscalzo J.
          Glucose-6-phosphate dehydrogenase deficiency promotes endothelial oxidant stress and decreases endothelial nitric oxide bioavailability.
          FASEB J. 2001; 15: 1771-1773
          • Weiss N.
          • Zhang Y.Y.S.
          • Heydrick C.
          • Bierl C.
          • Loscalzo J.
          Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction.
          Proc Natl Acad Sci USA. 2001; 98: 12503-12508
          • Battinelli E.M.
          • Willoughby S.R.
          • Foxall T.
          • Valeri C.R.
          • Loscalzo J.
          Induction of platelet formation from megakaryocytoid cells by nitric oxide.
          Proc Natl Acad Sci USA. 2001; 98: 14458-14462
          • Ignarro L.
          • Napoli C.N.
          • Loscalzo J.
          Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide.
          Circ Res. 2002; 90: 21-28
          • Forgione M.A.
          • Weiss N.
          • Heydrick S.
          • Cap A.
          • Klings E.S.
          • Bierl C.
          • Eberhardt R.T.
          • Farber H.W.
          • Loscalzo J.
          Cellular glutathione peroxidase deficiency and endothelial dysfunction.
          Am J Physiol. 2002; 282: H1255-H1261
          • Forgione M.A.
          • Cap A.
          • Liao R.
          • Moldovan N.I.
          • Eberhardt R.T.
          • Lim C.C.
          • Jones J.
          • Goldschmidt-Clermont P.J.
          • Loscalzo J.
          Heterozygous cellular glutathione peroxidase (GPx-1) deficiency in the mouse.
          Circulation. 2002; 106: 1154-1158
          • Forde P.
          • Scribner A.M.
          • Dial R.
          • Loscalzo J.
          • Trolliet M.R.
          Prevention of hypertension and renal dysfunction in Dahl rats by alpha-tocopherol.
          J Cardiovasc Pharm. 2003; 42: 82-88
          • Leopold J.A.
          • Walker J.
          • Scribner A.M.
          • Voetsch B.
          • Zhang Y.Y.
          • Loscalzo A.J.
          • Stanton R.C.
          • Loscalzo J.
          Glucose-6-phosphate dehydrogenase modulates vascular endothelial growth factor-mediated angiogenesis.
          J Biol Chem. 2003; 278: 32100-32106
          • Jain M.
          • Cui L.
          • Brenner D.A.
          • Wang B.
          • Handy D.E.
          • Leopold J.A.
          • Loscalzo J.
          • Apstein C.S.
          • Liao R.
          Increased myocardial dysfunction following ischemia-reperfusion in mice lacking glucose-6-phosphate dehydrogenase.
          Circulation. 2004; 109: 898-903
          • Walford G.A.
          • Mossignac R.L.
          • Scribner A.W.
          • Loscalzo J.
          • Leopold J.A.
          Hypoxia potentiates nitric oxide-mediated apoptosis in endothelial cells via peroxynitrite-induced activation of mitochondrial-dependent and -independent pathways.
          J Biol Chem. 2004; 279: 4425-4432
          • Jones J.E.
          • Walker J.L.
          • Song Y.
          • Weiss N.
          • Cardoso W.V.
          • Tuder R.M.
          • Loscalzo J.
          • Zhang Y.Y.
          Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats.
          Am J Physiol. 2004; 286: H1775-H1784
          • Bierl C.
          • Voetsch-Forgione B.
          • Jin R.
          • Handy D.
          • Loscalzo J.
          Determinants of human plasma glutathione peroxidase (GPx-3) expression.
          J Biol Chem. 2004; 279: 26839-26845
          • Farber H.
          • Loscalzo J.
          Pulmonary hypertension.
          N Engl J Med. 2004; 351: 1655-1665
          • Yang Y.
          • Loscalzo J.
          S-nitrosoprotein formation and localization in endothelial cells.
          Proc Natl Acad Sci USA. 2004; 102: 117-122
          • Handy D.E.
          • Zhang Y.
          • Loscalzo J.
          Homocysteine downregulates glutathione peroxidase (GPx1) by decreasing translation.
          J Biol Chem. 2005; 280: 15518-15525
          • Zhang Y.
          • Handy D.E.
          • Loscalzo J.
          Adenosine-dependent induction of glutathione peroxidase 1 (GPx-1) in human primary endothelial cells and protection against oxidative stress.
          Circ Res. 2005; 96: 831-837
          • Antman E.M.
          • DeMets D.
          • Loscalzo J.
          Cyclooxygenase inhibition and cardiovascular risk.
          Circulation. 2005; 112: 759-770