Ukr.Biochem.J. 2021; Volume 93, Issue 6, Nov-Dec, pp. 5-30

doi: https://doi.org/10.15407/ubj93.06.005

Biochemical and molecular-physiological aspects of the nitric oxide action in the utera

16.12.2021   Uncategorized   No comments

H. V. Danylovych, Yu. V. Danylovych

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: danylovych@biochem.kiev.ua

Received: 18 May 2021; Accepted: 12 November 2021

The sources of the nitric oxide (NO) formation in the uterus and the dynamics of changes in its content in different periods of organ functioning in human and animals are analyzed. The biochemical mechanisms of NO action on the myometrium contractile activity, the significance of NO in the physiological processes during pregnancy and labor, the importance of mitochondria as a reliable NO source in the smooth muscle and the possible ways of NO influence on Ca2+ transport and bioenergetic processes in mitochondria are considered. The authors’ data concerning ionic and membrane mechanisms of NO action on Ca2+-homeostasis of uterine myocytes, identification of nitric oxide in uterine smooth muscle mitochondria, biochemical characteristics of the NO-synthase reaction and the possible role of NO in the regulation of Ca2+ transport in these subcellular structures and in the electron transport chain functioning are presented and discussed.

Keywords: , , , ,

References:

  1. Treuer AV, Gonzalez DR. Nitric oxide synthases, S-nitrosylation and cardiovascular health: from molecular mechanisms to therapeutic opportunities (review). Mol Med Rep. 2015;11(3):1555-1565. PubMed, PubMedCentral, CrossRef
  2. Ghimire K, Altmann HM, Straub AC, Isenberg JS. Nitric oxide: what’s new to NO? Am J Physiol Cell Physiol. 2017;312(3):C254-C262. PubMed, PubMedCentral, CrossRef
  3. Bryan NS, Bian K, Murad F. Discovery of the nitric oxide signaling pathway and targets for drug development. Front Biosci (Landmark Ed). 2009;14:1-18. PubMed, CrossRef
  4. Philippu A. Nitric Oxide: A Universal Modulator of Brain Function. Curr Med Chem. 2016;23(24):2643-2652. PubMed, CrossRef
  5. Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, Zuppi C, Ghirlanda G. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud. 2010;7(1):15-25. PubMed, PubMedCentral, CrossRef
  6. Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol. 1997;272(2 Pt 2):R441-R463. PubMed, CrossRef
  7. Buxton ILO. Regulation of uterine function: a biochemical conundrum in the regulation of smooth muscle relaxation. Mol Pharmacol. 2004;65(5):1051-1059. PubMed, CrossRef
  8. López Bernal A. The regulation of uterine relaxation. Semin Cell Dev Biol. 2007;18(3):340-347. PubMed,  CrossRef
  9. Tiboni GM, Giampietro F, Lamonaca D. The soluble guanylate cyclase inhibitor methylene blue evokes preterm delivery and fetal growth restriction in a mouse model. In Vivo. 2001;15(4):333-337.  PubMed
  10. Bao S, Rai J, Schreiber J. Expression of nitric oxide synthase isoforms in human pregnant myometrium at term. J Soc Gynecol Investig. 2002;9(6):351-356. PubMed
  11. Siomek A. NF-κB signaling pathway and free radical impact. Acta Biochim Pol. 2012;59(3):323-331. PubMed
  12. Farina M, Ribeiro ML, Franchi A. Nitric oxide synthases in pregnant rat uterus. Reproduction. 2001;121(3):403-407. PubMed, CrossRef
  13. Okawa T, Vedernikov YP, Saade GR, Garfield RE. Effect of nitric oxide on contractions of uterine and cervical tissues from pregnant rats. Gynecol Endocrinol. 2004;18(4):186-193. PubMed, CrossRef
  14. Wray S, Prendergast C. The Myometrium: From Excitation to Contractions and Labour. In: Hashitani H., Lang R. (eds). Smooth Muscle Spontaneous Activity. Advances in Experimental Medicine and Biology. 2019; 1124.  CrossRef
  15. Buxton IL, Kaiser RA, Malmquist NA, Tichenor S. NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP. Br J Pharmacol. 2001;134(1):206-214. PubMed, PubMedCentral, CrossRef
  16. Valdés G, Corthorn J. Review: The angiogenic and vasodilatory utero-placental network. Placenta. 2011;32(Suppl 2):S170-S175.
    PubMed,  CrossRef
  17. Yellon SM, Mackler AM, Kirby MA. The role of leukocyte traffic and activation in parturition. J Soc Gynecol Investig. 2003;10(6):323-338. PubMed, CrossRef
  18. Danylovych IuV, Tuhai VA. Formation of NO and H2O2 in endometrial stromal cells under the effect of acetylcholine. Ukr Biokhim Zhurn. 2001;73(2):110-115. (In Ukrainian). PubMed
  19. Danylovych IuV. Effect of steroid hormones and oxytocin on NO and H2O2 production in the endometrium. Ukr Biokhim Zhurn. 2004;76(1):88-96. (In Ukrainian). PubMed
  20. Cameron IT, Campbell S. Nitric oxide in the endometrium. Hum Reprod Update. 1998;4(5):565-569. PubMed, CrossRef
  21. Khorram O, Garthwaite M, Magness RR. Endometrial and myometrial expression of nitric oxide synthase isoforms in pre- and postmenopausal women. J Clin Endocrinol Metab. 1999;84(6):2226-2232. PubMed, CrossRef
  22. Massmann GA, Mirabile CP, Figueroa JP. Nonpregnant sheep uterine type I and type III nitric oxide synthase expression is differentially regulated by estrogen. Biol Reprod. 1999;60(5):1198-1203. PubMed,  CrossRef
  23. Tota B, Quintieri AM, Angelone T. The emerging role of nitrite as an endogenous modulator and therapeutic agent of cardiovascular function. Curr Med Chem. 2010;17(18):1915-1925. PubMed, CrossRef
  24. Ghafourifar P, Cadenas E. Mitochondrial nitric oxide synthase. Trends Pharmacol Sci. 2005;26(4):190-195. PubMed, CrossRef
  25. Giulivi C, Kato K, Cooper CE. Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology. Am J Physiol Cell Physiol. 2006;291(6):C1225-C1231. PubMed,  CrossRef
  26. Zaobornyj T, Ghafourifar P. Strategic localization of heart mitochondrial NOS: a review of the evidence. Am J Physiol Heart Circ Physiol. 2012;303(11):H1283-H1293. PubMed, CrossRef
  27. Elfering SL, Sarkela TM, Giulivi C. Biochemistry of mitochondrial nitric-oxide synthase. J Biol Chem. 2002;277(41):38079-38086. PubMed, ], CrossRef
  28. Valdez LB, Zaobornyj T, Boveris A. Mitochondrial metabolic states and membrane potential modulate mtNOS activity. Biochim Biophys Acta. 2006;1757(3):166-172. PubMed, CrossRef
  29. Marsh N, Marsh  A. A short history of nitroglycerine and nitric oxide in pharmacology and physiology. Clin Exp Pharmacol Physiol. 2000;27(4):313-319.
    PubMed, CrossRef
  30. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357(Pt 3):593-615. PubMed, PubMedCentral, CrossRef
  31. Thomas DD, Liu X, Kantrow SP, Lancaster  JR Jr. The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci USA. 2001;98(1):355-360. PubMed, PubMedCentral, CrossRef
  32. Levine AB, Punihaole D, Levine TB. Characterization of the role of nitric oxide and its clinical applications. Cardiology. 2012;122(1):55-68. PubMed, CrossRef
  33. Zhao Y, Vanhoutte PM, Leung SWS. Vascular nitric oxide: Beyond eNOS. J Pharmacol Sci. 2015;129(2):83-94. PubMed, CrossRef
  34. Reutov VP. Nitric oxide cycle in mammals and the cyclicity principle. Biochemistry (Mosc). 2002;67(3):293-311. (In Russian). PubMed, CrossRef
  35. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829-837. PubMed, PubMedCentral, CrossRef
  36. Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999;43(3):521-531. PubMed, CrossRef
  37. Daff S. NO synthase: structures and mechanisms. Nitric Oxide. 2010;23(1):1-11. PubMed, CrossRef
  38. Nosarev AV, Smagliy LV, Anfinogenova Y, Popov SV, Kapilevich LV. Exercise and NO production: relevance and implications in the cardiopulmonary system. Front Cell Dev Biol. 2015;2:73. PubMed, PubMedCentral, CrossRef
  39. Förstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions.  Hypertension. 1994;23(6 Pt 2):1121-1131. PubMed, CrossRef
  40. Carreras MC, Poderoso JJ. Mitochondrial nitric oxide in the signaling of cell integrated responses. Am J Physiol Cell Physiol. 2007;292(5):C1569-C1580. PubMed, CrossRef
  41. Tsai KD, Chen W, Wang SH, Hsiao YW, Chi JY, Wu HY, Lee YJ, Wong HY, Tseng MJ, Lin TH. Downregulation of connective tissue growth factor by LPS/IFN-γ-induced nitric oxide is reversed by aristolochic acid treatment in glomerular mesangial cells via STAT-1α and NF-κB signaling. Chem Biol Interact. 2014;210:86-95. PubMed, CrossRef
  42. Tripathi P. Nitric oxide and immune response. Indian J Biochem Biophys. 2007;44(5):310-319. PubMed
  43. Tengan CH, Rodrigues GS, Godinho RO.Nitric oxide in skeletal muscle: role on mitochondrial biogenesis and function. Int J Mol Sci. 2012;13(12):17160-17184. PubMed, PubMedCentral, CrossRef
  44. Ogura T, Yokoyama T, Fujisawa H, Kurashima Y, Esumi H. Structural diversity of neuronal nitric oxide synthase mRNA in the nervous system. Biochem Biophys Res Commun. 1993;193(3):1014-1022. PubMed, CrossRef
  45. Silvagno F, Xia H, Bredt DS. Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle. J Biol Chem. 1996;271(19):11204-11208. PubMed, CrossRef
  46. Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996;84(5):757-767.
    PubMed,  CrossRef
  47. Brenman JE, Xia H, Chao DS, Black SM, Bredt DS. Regulation of neuronal nitric oxide synthase through alternative transcripts. Dev Neurosci. 1997;19(3):224-231. PubMed, CrossRef
  48. Kone BC, Kuncewicz T, Zhang W, Yu ZY. Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide. Am J Physiol Renal Physiol. 2003;285(2):F178-F190. PubMed, CrossRef
  49. Duan W, Zhou J, Li W, Zhou T, Chen Q, Yang F, Wei T. Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase. Protein Cell. 2013;4(4):286-298. PubMed, PubMedCentral, CrossRef
  50. Heinonen I, Saltin  B, Hellsten  Y, Kalliokoski KK. The effect of nitric oxide synthase inhibition with and without inhibition of prostaglandins on blood flow in different human skeletal muscles. Eur J Appl Physiol. 2017;117(6):1175-1180. PubMed, CrossRef
  51. Li Q, Chen Y, Zhang X, Zuo S, Ge H, Chen Y, Liu X, Zhang JH, Ruan H, Feng H. Scutellarin attenuates vasospasm through the Erk5-KLF2-eNOS pathway after subarachnoid hemorrhage in rats. J Clin Neurosci. 2016;34:264-270. PubMed, CrossRef
  52. Durán WN, Breslin JW, Sánchez FA. The NO cascade, eNOS location, and microvascular permeability. Cardiovasc Res. 2010;87(2):254-261. PubMed, PubMedCentral, CrossRef
  53. Lee JE, Yuan H, Liang FX, Sehgal PB. Nitric oxide scavenging causes remodeling of the endoplasmic reticulum, Golgi apparatus and mitochondria in pulmonary arterial endothelial cells. Nitric Oxide. 2013;33:64-73. PubMed, PubMedCentral, CrossRef
  54. Shaul PW, Smart EJ, Robinson LJ, German Z, Yuhanna IS, Ying Y, Anderson RG, Michel T. Acylation targets emdothelial nitric-oxide synthase to plasmalemmal caveolae. J Biol Chem. 1996;271(11):6518-6522. PubMed, CrossRef
  55. Davidson SM, Duchen MR. Effects of NO on mitochondrial function in cardiomyocytes: Pathophysiological relevance. Cardiovasc Res. 2006;71(1):10-21.
    PubMed, CrossRef
  56. Komeima K, Hayashi Y, Naito Y, Watanabe Y. Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells. J Biol Chem. 2000;275(36):28139-28143. PubMed, CrossRef
  57. Litvinova L, Atochin DN, Fattakhov N, Vasilenko M, Zatolokin P, Kirienkova E. Nitric oxide and mitochondria in metabolic syndrome. Front Physiol. 2015;6:20. PubMed, PubMedCentral, CrossRef
  58. Franco MC, Arciuch VGA, Peralta JG, Galli S, Levisman D, López LM, Romorini L, Poderoso JJ, Carreras MC. Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase. J Biol Chem. 2006;281(8):4779-4786. PubMed, CrossRef
  59. Nagano T, Fridovich I. The co-oxidation of ammonia to nitrite during the aerobic xanthine oxidase reaction. Arch Biochem Biophys. 1985;241(2):596-601. PubMed, CrossRef
  60. Dull BJ, Hotchkiss JH. Activated oxygen and mammalian nitrate biosynthesis. Carcinogenesis. 1984;5(9):1161-1164. PubMed, CrossRef
  61. Guerra DD, Hurt KJ. Gasotransmitters in pregnancy: from conception to uterine involution. Biol Reprod. 2019;101(1):4-25. PubMed, PubMedCentral, CrossRef
  62. Omar SA, Webb AJ, Lundberg JO, Weitzberg E. Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases. J Intern Med. 2016;279(4):315-336. PubMed, CrossRef
  63. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156-167. PubMed, CrossRef
  64. Sybirna NO, Lyuta MYa, Klymyshyn NI. Mоlecular mechanisms of nitric oxide deposition in erythrocytes.  Biol Stud.  2010; 4(1): 143–160. (Іn Ukrainian). CrossRef
  65. Shiva S. Mitochondria as metabolizers and targets of nitrite. Nitric Oxide. 2010;22(2):64-74. PubMed, PubMedCentral, CrossRef
  66. Shiva S. Nitrite: A Physiological Store of Nitric Oxide and Modulator of Mitochondrial Function. Redox Biol. 2013;1(1):40-44. PubMed, PubMedCentral, CrossRef
  67. Siervo M, Scialò F, Shannon OM, Stephan BCM, Ashor AW. Does dietary nitrate say NO to cardiovascular ageing? Current evidence and implications for research. Proc Nutr Soc. 2018;77(2):112-123. PubMed, CrossRef
  68. Fernando V, Zheng X, Walia Y, Sharma V, Letson J, Furuta S. S-Nitrosylation: An Emerging Paradigm of Redox Signaling. Antioxidants (Basel). 2019;8(9):404. PubMed, PubMedCentral, CrossRef
  69. Liu C, Liang MC, Soong TW. Nitric Oxide, Iron and Neurodegeneration. Front Neurosci. 2019;13:114. PubMed, PubMedCentral, CrossRef
  70. Kleschyov AL. The NO-heme signaling hypothesis.  Free Radic Biol Med. 2017;112:544-552. PubMed, CrossRef
  71. Corbin JD. Mechanisms of action of PDE5 inhibition in erectile dysfunction. Int J Impot Res. 2004;16(Suppl 1):S4-S7. PubMed,  CrossRef
  72. Leite ACR, Oliveira HCF, Utino FL, Garcia R, Alberici LC, Fernandes MP, Castilho RF, Vercesi AE. Mitochondria generated nitric oxide protects against permeability transition via formation of membrane protein S-nitrosothiols. Biochim Biophys Acta. 2010;1797(6-7):1210-1216. PubMed, CrossRef
  73. Ulrich C, Quilici DR, Schlauch KA, Buxton ILO. The human uterine smooth muscle S-nitrosoproteome fingerprint in pregnancy, labor, and preterm labor. Am Ш2013;305(8):C803-C816. PubMed, PubMedCentral, CrossRef
  74. Garfield RE, Saade G, Buhimsch C, Buhimschi I, Shi L, Shi SQ, Chwalisz K. Control and assessment of the uterus and cervix during pregnancy and labour. Hum Reprod Update. 1998;4(5):673-695. PubMed, CrossRef
  75. Bulbul A, Yağci A, Altunbaş K, Sevimli A, Celik HA, Karadeniz A, Akdağ E. The role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats. Theriogenology. 2007;68(8):1156-1168.  pm id=”17869333″], CrossRef
  76. Ravanos K, Dagklis T, Petousis S, Margioula-Siarkou C, Prapas Y, Prapas N. Factors implicated in the initiation of human parturition in term and preterm labor: a review. Gynecol Endocrinol. 2015;31(9):679-683. PubMed, CrossRef
  77. Aguilar HN, Mitchell BF. Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update. 2010;16(6):725-744. PubMed, CrossRef
  78. Nadeem L, Shynlova O, Mesiano S, Lye S. Progesterone Via its Type-A Receptor Promotes Myometrial Gap Junction Coupling. Sci Rep. 2017;7(1):13357. PubMed, PubMedCentral, CrossRef
  79. Mitchell BF, Aguilar HN, Mosher A, Wood S, Slater DM. The uterine myocyte as a target for prevention of preterm birth. Facts Views Vis Obgyn. 2013;5(1):72-81. PubMed, PubMedCentral
  80. Chalmers S, Olson ML, MacMillan D, Rainbow RD, McCarron JG. Ion channels in smooth muscle: regulation by the sarcoplasmic reticulum and mitochondria. Cell Calcium. 2007;42(4-5):447-466. PubMed, CrossRef
  81. Trebak M, Ginnan R, Singer HA, Jourd’heuil D. Interplay between calcium and reactive oxygen/nitrogen species: an essential paradigm for vascular smooth muscle signaling. Antioxid Redox Signal. 2010;12(5):657-674. PubMed, PubMedCentral, CrossRef
  82. Aguilar HN, Tracey CN, Zielnik B, Mitchell BF. Rho-kinase mediates diphosphorylation of myosin regulatory light chain in cultured uterine, but not vascular smooth muscle cells. J Cell Mol Med. 2012;16(12):2978-2989. PubMed, PubMedCentral, CrossRef
  83. Smeazzetto S, Armanious GP, Moncelli MR, Bak JJ, Lemieux MJ, Young HS, Tadini-Buoninsegni F. Conformational memory in the association of the transmembrane protein phospholamban with the sarcoplasmic reticulum calcium pump SERCA. J Biol Chem. 2017;292(52):21330-21339. PubMed, PubMedCentral, CrossRef
  84. Tarasova NV, Vishnyakova PA, Logashina YA, Elchaninov AV. Mitochondrial Calcium Uniporter Structure and Function in Different Types of Muscle Tissues in Health and Disease. Int J Mol Sci. 2019;20(19):4823. PubMed, PubMedCentral, CrossRef
  85. Malli R, Graier WF. Mitochondrial Ca2+ channels: Great unknowns with important functions. FEBS Lett. 2010;584(10):1942-1947. PubMed, PubMedCentral, CrossRef
  86. Toda N, Toda H, Okamura T. Regulation of myometrial circulation and uterine vascular tone by constitutive nitric oxide. Eur J Pharmacol. 2013;714(1-3):414-423. PubMed, CrossRef
  87. Norman JE, Cameron IT. Nitric oxide in the human uterus. Rev Reprod. 1996;1(1):61-68. PubMed, CrossRef
  88. Zullino S, Buzzella F , Simoncini T. Nitric oxide and the biology of pregnancy. Vascul Pharmacol. 2018;110:71-74. PubMed, CrossRef
  89.  Xiao D, Pearce WJ, Zhang L. Pregnancy enhances endothelium-dependent relaxation of ovine uterine artery: role of NO and intracellular Ca(2+). Am J Physiol Heart Circ Physiol. 2001;281(1):H183-H190. PubMed, CrossRef
  90. Danylovych IuV. Mechanisms of acetylcholine-dependent production of H2O2 and NO2- by stromal cells of endometrium. Ukr Biokhim Zhurn. 2003;75(5):77-84. (In Ukrainian). PubMed
  91. Arthur P, Taggart MJ, Zielnik B, Wong S, Mitchell BF. Relationship between gene expression and function of uterotonic systems in the rat during gestation, uterine activation and both term and preterm labour. J Physiol. 2008;586(24):6063-6076. PubMed, PubMedCentral, CrossRef
  92. Li Y, Zhou X, Wei QW, Huang RH, Shi FX. Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and soluble guanylyl cyclase α and β subunits in postnatal porcine uteri. Acta Histochem. 2014;116(3):466-473. PubMed, CrossRef
  93. Buhimschi IA, Saade GR, Chwalisz K, Garfield RE. The nitric oxide pathway in pre-eclampsia: pathophysiological implications. Hum Reprod Update. 1998;4(1):25-42. PubMed, CrossRef
  94. Tiboni GM, Corso AD, Marotta F. Progestational agents prevent preterm birth induced by a nitric oxide synthesis inhibitor in the mouse. In Vivo. 2008;22(4):447-450. PubMed
  95. Rytlewski K, Olszanecki R, Lauterbach R, Grzyb A, Kiec-Wilk B, Dembinska-Kiec A, Basta A. Effects of oral L-arginine on the pulsatility indices of umbilical artery and middle cerebral artery in preterm labor. Eur J Obstet Gynecol Reprod Biol. 2008;138(1):23-28.  PubMed, CrossRef
  96. Aljameil N, Tabassum H, AlMayouf H, Alshenefy A, Almohizea MM, Ali M N. Identification of serum cytokines as markers in women with recurrent pregnancy loss or miscarriage using MILLIPLEX analysis. Biomed Res. 2018;29(18):3512-3517.
  97. Javadi-Paydar M, Lesani A, Vakilipour R, Ghazi P, Tavangar SM,  Hantoushzadeh S, Norouzi A, Dehpour AR. Evaluation of the tocolytic effect of morphine in a mouse model of lipopolysaccharide-induced preterm delivery: the role of nitric oxide. Eur J Obstet Gynecol Reprod Biol. 2009;147(2):166-172. PubMed, CrossRef
  98. Ramesh S, Morrell CN, Tarango C, Thomas GD, Yuhanna IS, Girardi G, Herz J, Urbanus RT, de Groot PG, Thorpe PE, Salmon JE, Shaul PW, Mineo C. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2. J Clin Invest. 2011;121(1):120-131. PubMed, PubMedCentral, CrossRef
  99. Miranda S, Billoir P, Damian L, Thiebaut PA, Schapman D, Le Besnerais M , Jouen F, Galas L, Levesque H, Le Cam-Duchez V, Joannides R, Richard V, Benhamou Y. Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction. PLoS One. 2019;14(3):e0212614. PubMed, PubMedCentral, CrossRef
  100. Buttery LD, McCarthy A, Springall DR, Sullivan MH, Elder MG, Michel T, Polak JM. Endothelial nitric oxide synthase in the human placenta: regional distribution and proposed regulatory role at the feto-maternal interface. Placenta. 1994;15(3):257-265.  PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.