Dr. Joseph Loscalzo (M.D., 1978; Ph.D., 1977) is recognized here as a Redox Pioneer because he has published two articles in the field of antioxidant/redox biology that have been cited more than 1,000 times and 22 articles that have been cited more than 100 times. Dr. Loscalzo is known for his seminal contributions to our understanding of the vascular biology of nitric oxide. His initial discovery that the antiplatelet effects of organic nitrates are potentiated by thiols through a mechanism that involved metabolism to S-nitrosothiols was followed by the demonstration that S-nitrosothiols are formed endogenously through S-transnitrosation, stabilize nitric oxide, and facilitate the transport and transfer of nitric oxide between and within cells of the vessel wall. These properties led to the development of S-nitrosothiol–containing pharmacotherapies to treat disease states characterized by nitric oxide deficiency. Dr. Loscalzo's other scientific contributions include identifying the vascular functional consequences of genetic deficiencies of antioxidant enzymes that decrease nitric oxide bioavailability, collectively termed the “oxidative enzymopathies,” and demonstrating the role of mitochondria in modulating the disulfide subproteome, and in redox signaling in hypoxia. He has received numerous awards and honors for his scientific contributions, including election to the Institute of Medicine of the National Academy of Sciences. Antioxid. Redox Signal. 13, 1125–1132.
BattinelliE, WilloughbySR, FoxallT, ValeriCR, LoscalzoJ. Induction of platelet formation from megakaryocytoid cells by nitric oxide. Proc Natl Acad Sci U S A, 98:14458–14463. 2001.
3.
ChanSY, LoscalzoJ. MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle, 9:1072–1083. 2010.
4.
ChanSY, ZhangYY, HemannC, MahoneyCE, ZweierJL, LoscalzoJ. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab, 10:273–284. 2009.
5.
EberhardtRT, ForgioneMA, CapA, LeopoldJA, RuddMA, TrollietM, HeydrickS, StarkR, KlingsES, MoldovanNI, YaghoubiM, Goldschmidt-ClermontPJ, FarberHW, CohenR, LoscalzoJ. Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia. J Clin Invest, 106:483–491. 2000.
ForgioneMA, CapA, LiaoR, MoldovanNI, EberhardtRT, LimCC, JonesJ, Goldschmidt-ClermontPJ, LoscalzoJ. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure. Circulation, 106:1154–1158. 2002.
FreedmanJE, FreiB, WelchGN, LoscalzoJ. Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols. J Clin Invest, 96:394–400. 1995.
10.
FreedmanJE, LoscalzoJ, BarnardMR, AlpertC, KeaneyJF, MichelsonAD. Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Invest, 100:350–356. 1997.
11.
FreedmanJE, LoscalzoJ, BenoitSE, ValeriCR, BarnardMR, MichelsonAD. Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis. J Clin Invest, 97:979–987. 1996.
12.
FreedmanJE, SauterR, BattinelliEM, AultK, KnowlesC, HuangPL, LoscalzoJ. Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res, 84:1416–1421. 1999.
13.
FreedmanJE, TingB, HankinB, LoscalzoJ, KeaneyJFJr, VitaJA. Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes. Circulation, 98:1481–1486. 1998.
JonesJE, WalkerJL, SongY, WeissN, CardosoWV, TuderRM, LoscalzoJ, ZhangYY. Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol, 286:H1775–H1784. 2004.
LoscalzoJ. N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. J Clin Invest, 76:703–708. 1985.
23.
MaronBA, ZhangYY, HandyDE, BeuveA, TangSS, LoscalzoJ, LeopoldJA. Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells. J Biol Chem, 284:7665–7672. 2009.
24.
MendelsohnME, O'NeillS, GeorgeD, LoscalzoJ. Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine. J Biol Chem, 265:19028–19034. 1990.
25.
MichelsonAD, BenoitSE, FurmanMI, BreckwoldtWL, RohrerMJ, BarnardMR, LoscalzoJ. Effects of nitric oxide/EDRF on platelet surface glycoproteins. Am J Physiol, 270:H1640–H1648. 1996.
RovinJD, StamlerJS, LoscalzoJ, FoltsJD. Sodium nitroprusside, an endothelium-derived relaxing factor congener, increases platelet cyclic GMP levels and inhibits epinephrine-exacerbated in vivo platelet thrombus formation in stenosed canine coronary arteries. J Cardiovasc Pharmacol, 22:626–631. 1993.
28.
ScharfsteinJS, KeaneyJFJr, SlivkaA, WelchGN, VitaJA, StamlerJS, LoscalzoJ. In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols. J Clin Invest, 94:1432–1439. 1994.
29.
SimonDI, StamlerJS, JarakiO, KeaneyJF, OsborneJA, FrancisSA, SingelDJ, LoscalzoJ. Antiplatelet properties of protein S-nitrosothiols derived from nitric oxide and endothelium-derived relaxing factor. Arterioscler Thromb, 13:791–799. 1993.
30.
SimonDI, StamlerJS, LohE, LoscalzoJ, FrancisSA, CreagerMA. Effect of nitric oxide synthase inhibition on bleeding time in humans. J Cardiovasc Pharmacol, 26:339–342. 1995.
31.
SongY, ColemanL, ShiJ, BeppuH, SatoK, WalshK, LoscalzoJ, ZhangYY. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol, 295:H677–690. 2008.
32.
SongY, JonesJE, BeppuH, KeaneyJFJr, LoscalzoJ, ZhangYY. Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation, 112:553–562. 2005.
StamlerJS, JarakiO, OsborneJ, SimonDI, KeaneyJ, VitaJ, SingelD, ValeriCR, LoscalzoJ. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA, 89:7674–7677. 1992.
35.
StamlerJS, SingelDJ, LoscalzoJ. Biochemistry of nitric oxide and its redox-activated forms. Science, 258:1898–1902. 1992.
36.
StamlerJS, VaughanDE, LoscalzoJ. Synergistic disaggregation of platelets by tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin. Circ Res, 65:796–804. 1989.
37.
VoetschB, JinRC, BierlC, BenkeKS, KenetG, SimioniP, OttavianoF, DamascenoBP, Annichino-BizacchiJM, HandyDE, LoscalzoJ. Promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene: a novel risk factor for arterial ischemic stroke among young adults and children. Stroke, 38:41–49. 2007.
38.
VoetschB, JinRC, BierlC, Deus-SilvaL, CamargoEC, Annichino-BizacchiJM, HandyDE, LoscalzoJ. Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis. Stroke, 39:303–307. 2008.
39.
WalfordGA, MoussignacRL, ScribnerAW, LoscalzoJ, LeopoldJA. Hypoxia potentiates nitric oxide-mediated apoptosis in endothelial cells via peroxynitrite-induced activation of mitochondria-dependent and -independent pathways. J Biol Chem, 279:4425–4432. 2004.
40.
WalkerJL, LoscalzoJ, ZhangYY. 5-Lipoxygenase and human pulmonary artery endothelial cell proliferation. Am J Physiol Heart Circ Physiol, 282:H585–H593. 2002.
41.
WeissN, HeydrickS, ZhangYY, BierlC, CapA, LoscalzoJ. Cellular redox state and endothelial dysfunction in mildly hyperhomocysteinemic cystathionine beta-synthase-deficient mice. Arterioscler Thromb Vasc Biol, 22:34–41. 2002.
YangY, LoscalzoJ. S-Nitrosoprotein formation and localization in endothelial cells. Proc Natl Acad Sci U S A, 102:117–122. 2005.
44.
YangY, SongY, LoscalzoJ. Regulation of the protein disulfide proteome by mitochondria in mammalian cells. Proc Natl Acad Sci USA, 104:10813–10817. 2007.
45.
ZaiA, RuddMA, ScribnerAW, LoscalzoJ. Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide. J Clin Invest, 103:393–399. 1999.
46.
ZhangYY, WalkerJL, HuangA, KeaneyJF, ClishCB, SerhanCN, LoscalzoJ. Expression of 5-lipoxygenase in pulmonary artery endothelial cells. Biochem J, 361:267–276. 2002.
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