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Malaria link of hypertension: a hidden syndicate of angiotensin II, bradykinin and sphingosine 1-phosphate

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Abstract

In malaria-endemic countries, the burden of hypertension is on the rise. Although malaria and hypertension seem to have no direct link, several studies in recent years support their possible link. Three bioactive molecules such as angiotensin II (Ang II), bradykinin (BK) and sphingosine 1-phosphate (S1P) are crucial in regulating blood pressure. While the increased level of Ang II and S1P are responsible for inducing hypertension, BK is arthero-protective and anti-hypertensive. Therefore, in the present review, based on available literatures we highlight the present knowledge on the production and bioavailability of these molecules, the mechanism of their regulation of hypertension, and patho-physiological role in malaria. Further, a possible link between malaria and hypertension is hypothesized through various arguments based on experimental evidence. Understanding of their mechanisms of blood pressure regulation during malaria infection may open up avenues for drug therapeutics and management of malaria in co-morbidity with hypertension.

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References

  1. Dhangadamajhi G, Kar SK, Ranjit M. The survival strategies of malaria parasite in the red blood cell and host cell polymorphisms. Malar Res Treat. 2010;2010.

  2. Sahu PK, Satpathi S, Behera PK, Mishra SK, Mohanty S, Wassmer SC. Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches. Front Cell Infect Microbiol. 2015;5:75.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sypniewska P, Duda JF, Locatelli I, Althaus CR, Althaus F, Genton B. Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis. BMC Med. 2017;15(1):147.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan MJ, et al. National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 54 million participants. The Lancet. 2011;377(9765):568–77.

    Article  Google Scholar 

  5. Zhou B, Danaei G, Stevens GA, Bixby H, Taddei C, Carrillo-Larco RM, et al. Long-term and recent trends in hypertension awareness, treatment, and control in 12 high-income countries: an analysis of 123 nationally representative surveys. The Lancet. 2019;394(10199):639–51.

    Article  Google Scholar 

  6. Dhangadamajhi G, Mohapatra BN, Kar SK, Ranjit M. Gene polymorphisms in angiotensin I converting enzyme (ACE I/D) and angiotensin II converting enzyme (ACE2 C→ T) protect against cerebral malaria in Indian adults. Infect Genet Evol. 2010;10(2):337–41.

    Article  CAS  PubMed  Google Scholar 

  7. Etyang AO, Kapesa S, Odipo E, Bauni E, Kyobutungi C, Abdalla M, et al. Effect of previous exposure to malaria on blood pressure in Kilifi, Kenya: a Mendelian randomization study. J Am Heart Assoc. 2019;8(6):e011771.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Etyang AO, Smeeth L, Cruickshank JK, Scott JAG. The malaria-high blood pressure hypothesis. Circ Res. 2016;119(1):36–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Eze IC, Bassa FK, Essé C, Koné S, Acka F, Laubhouet-Koffi V, et al. Epidemiological links between malaria parasitaemia and hypertension: findings from a population-based survey in rural Côte d’Ivoire. J Hypertens. 2019;37(7):1384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gallego-Delgado J, Walther T, Rodriguez A. The high blood pressure-malaria protection hypothesis. Circ Res. 2016;119(10):1071–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Volpe M, Battistoni A. An evolutionary rebus: the complex link between malaria and hypertension. J Hypertens. 2019;37(7):1344–6.

    Article  CAS  PubMed  Google Scholar 

  12. Don-Doncow N, Zhang Y, Matuskova H, Meissner A. The emerging alliance of sphingosine-1-phosphate signalling and immune cells: from basic mechanisms to implications in hypertension. Br J Pharmacol. 2019;176(12):1989–2001.

    Article  CAS  PubMed  Google Scholar 

  13. Nwokocha CR, Bafor EE, Ajayi OI, Ebeigbe AB. The malaria-high blood pressure hypothesis: revisited. Am J Hypertens. 2020;

  14. Koopman JJ, van Bodegom D, Jukema JW, Westendorp RG. Risk of cardiovascular disease in a traditional African population with a high infectious load: a population-based study. PLoS ONE. 2012;7(10):e46855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kearney PM, Whelton M, Reynolds K, Whelton PK, He J. Worldwide prevalence of hypertension: a systematic review. J Hypertens. 2004;22(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  16. Adam I, Elhassan EM, Mohmmed AA, Salih MM, Elbashir MI. Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan. Malar J. 2011;10(1):258.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. BJOG Int J Obstet Gynaecol. 1992;99(7):547–53.

    Article  CAS  Google Scholar 

  18. Ndao CT, Dumont A, Fievet N, Doucouré S, Gaye A, Lehesran J-Y. Placental malarial infection as a risk factor for hypertensive disorders during pregnancy in Africa: a case-control study in an urban area of Senegal West Africa. Am J Epidemiol. 2009;170(7):847–53.

    Article  CAS  PubMed  Google Scholar 

  19. Law C, Shiell A, Newsome C, Syddall H, Shinebourne E, Fayers P, et al. Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation. 2002;105(9):1088–92.

    Article  CAS  PubMed  Google Scholar 

  20. Ayoola OO, Omotade OO, Gemmell I, Clayton PE, Cruickshank JK. The impact of malaria in pregnancy on changes in blood pressure in children during their first year of life. Hypertension. 2014;63(1):167–72.

    Article  CAS  PubMed  Google Scholar 

  21. Cruickshank J, Mzayek F, Liu L, Kieltyka L, Sherwin R, Webber L, et al. Origins of the “black/white” difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study. Circulation. 2005;111(15):1932–7.

    Article  CAS  PubMed  Google Scholar 

  22. Cappuccio FP. Ethnicity and cardiovascular risk: variations in people of African ancestry and South Asian origin. J Hum Hypertens. 1997;11(9):571–6.

    Article  CAS  PubMed  Google Scholar 

  23. Sampson UK, Edwards TL, Jahangir E, Munro H, Wariboko M, Wassef MG, et al. Factors associated with the prevalence of hypertension in the southeastern United States: insights from 69 211 blacks and whites in the southern community cohort study. Circ Cardiovasc Qual Outcomes. 2014;7(1):33–54.

    Article  PubMed  Google Scholar 

  24. Ferrari R, et al. RAAS inhibition and mortality in hypertension: from pharmacology to clinical evidence. 2013;

  25. Intapad S. Sphingosine-1-phosphate signaling in blood pressure regulation. Am J Physiol-Ren Physiol. 2019;317(3):F638–40.

    Article  CAS  Google Scholar 

  26. Katsi V, Katsimichas T, Pittaras A, Grassos C, Katsimichas A, Tousoulis D, et al. Hypertension and bradykinin: a dangerous affair? Cardiovasc Endocrinol Metab. 2012;1(2):24–30.

    Article  CAS  Google Scholar 

  27. Foulquier S, Paulis L, Kaschina E, Namsolleck P, Unger T. Hormonal systems. In: Disorders of Blood Pressure Regulation. Springer; 2018. p. 81–106.

  28. te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AJ. Hypertension: renin–angiotensin–aldosterone system alterations. Circ Res. 2015;116(6):960–75.

    Article  Google Scholar 

  29. van Kats JP, de Lannoy LM, Danser AJ, van Meegen JR, Verdouw PD, Schalekamp MA. Angiotensin II Type 1 (AT1) receptor–mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo. Hypertension. 1997;30(1):42–9.

    Article  PubMed  Google Scholar 

  30. Gebre AK, Altaye BM, Atey TM, Tuem KB, Berhe DF. Targeting renin-angiotensin system against Alzheimer’s disease. Front Pharmacol. 2018;9:440.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Royea J, Hamel E. Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets. GeroScience. 2020;1–20.

  32. Wright JW, Harding JW. Contributions by the brain renin-angiotensin system to memory, cognition, and Alzheimer’s disease. J Alzheimers Dis. 2019;67(2):469–80.

    Article  PubMed  Google Scholar 

  33. Khalil RA. Hypertension and vascular dysfunction. In: Interdisciplinary concepts in cardiovascular health. Springer; 2013. p. 1–37.

  34. Laurent S, Chatellier G, Azizi M, Calvet D, Choukroun G, Danchin N, et al. Protocol of the SPARTE study: a strategy for preventing cardiovascular and renal events based on arterial stiffness. Artery Res. 2020;

  35. Kaschina E, Unger T. Prehypertension and the renin-angiotensin-aldosterone system. In: Prehypertension and cardiometabolic syndrome. Springer; 2019. p. 307–18.

  36. Liu M, Solomon W, Cespedes JC, Wilson NO, Ford B, Stiles JK. Neuregulin-1 attenuates experimental cerebral malaria (ECM) pathogenesis by regulating ErbB4/AKT/STAT3 signaling. J Neuroinflammation. 2018;15(1):104.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Norlander AE, Saleh MA, Kamat NV, Ko B, Gnecco J, Zhu L, et al. Interleukin-17A regulates renal sodium transporters and renal injury in angiotensin II–induced hypertension. Hypertension. 2016;68(1):167–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Silva LS, Peruchetti DB, Silva-Aguiar RP, Abreu TP, Dal-Cheri BK, Takiya CM, et al. The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney injury. PLoS ONE. 2018;13(9):e0203836.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Gallego-Delgado J, Basu-Roy U, Ty M, Alique M, Fernandez-Arias C, Movila A, et al. Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria. J Clin Invest. 2016;126(10):4016–29.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Silva-Filho JL, Caruso-Neves C, Pinheiro AA. Targeting angiotensin II type-1 receptor (AT1R) inhibits the harmful phenotype of Plasmodium-specific CD8+ T cells during blood-stage malaria. Front Cell Infect Microbiol. 2017;7:42.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Silva-Filho JL, Caruso-Neves C, Pinheiro AAS. Angiotensin II type-1 receptor (AT 1 R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells. Sci Rep. 2016;6:35997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Silva-Filho JL, Souza MC, Ferreira-DaSilva CT, Silva LS, Costa MFS, Padua TA, et al. Angiotensin II is a new component involved in splenic T lymphocyte responses during Plasmodium berghei ANKA infection. PLoS ONE. 2013;8(4):e62999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Maciel C, de Oliveira Junior VX, Fazio MA, Nacif-Pimenta R, Miranda A, Pimenta PF, et al. Anti-plasmodium activity of angiotensin II and related synthetic peptides. PLoS ONE. 2008;3(9):e3296.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Saraiva VB, de Souza SL, Ferreira-DaSilva CT, da Silva-Filho JL, Teixeira-Ferreira A, Perales J, et al. Impairment of the Plasmodium falciparum erythrocytic cycle induced by angiotensin peptides. PLoS ONE. 2011;6(2):e17174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gallego-Delgado J, Baravian C, Edagha I, Ty MC, Ruiz-Ortega M, Xu W, et al. Angiotensin II moderately decreases plasmodium infection and experimental cerebral malaria in mice. PLoS ONE. 2015;10(9):e0138191.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bala R, Abdulazeez A, Kiru A, Abdullahi N, Abubakar B. Effect of an angiotensin converting enzyme inhibitor (Captopril) on liver and kidney function parameters in plasmodium berghei-infected mice. J Adv Med Pharm Sci. 2018;1–8.

  47. Hoffmann BR, Stodola TJ, Wagner JR, Didier DN, Exner EC, Lombard JH, et al. Mechanisms of Mas1 receptor-mediated signaling in the vascular endothelium. Arterioscler Thromb Vasc Biol. 2017;37(3):433–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F, Adam A. The kallikrein-kinin system: current and future pharmacological targets. J Pharmacol Sci. 2005;99(1):6–38.

    Article  CAS  PubMed  Google Scholar 

  49. Bagnaresi P, Barros NM, Assis DM, Melo PM, Fonseca RG, Juliano MA, et al. Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins. Malar J. 2012;11(1):156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Silva LS, Pinheiro AS, Teixeira DE, Silva-Aguiar RP, Peruchetti DB, Scharfstein J, et al. Kinins released by erythrocytic stages of Plasmodium falciparum enhance adhesion of infected erythrocytes to endothelial cells and increase blood brain barrier permeability via activation of bradykinin receptors. Front Med. 2019;6:75.

    Article  Google Scholar 

  51. Ventura PD, Carvalho CP, Barros NM, Martins-Silva L, Dantas EO, Martinez C, et al. Malaria infection promotes a selective expression of kinin receptors in murine liver. Malar J. 2019;18(1):213.

    Article  PubMed  PubMed Central  Google Scholar 

  52. de Souza SL, de Barros PD, Ferreira-Da Silva CT, Ferreira-DaSilva AT, Perales J, Caruso-Neves C, et al. Interaction between bradykinin B2 and Ang-(1–7) Mas receptors regulates erythrocyte invasion by Plasmodium falciparum. Biochim Biophys Acta BBA-Gen Subj. 2016;1860(11):2438–44.

    Article  Google Scholar 

  53. de Moraes LV, Barateiro A, Sousa PM, Penha-Gonçalves C. Bradykinin sequestration by Plasmodium berghei infected erythrocytes conditions B2R signaling and parasite uptake by fetal trophoblasts. Front Microbiol. 2018;9:3106.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Singh S, Chitnis CE. Molecular signaling involved in entry and exit of malaria parasites from host erythrocytes. Cold Spring Harb Perspect Med. 2017;7(10):a026815.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Książek M, Chacińska M, Chabowski A, Baranowski M. Sources, metabolism, and regulation of circulating sphingosine-1-phosphate. J Lipid Res. 2015;56(7):1271–81.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dhangadamajhi G, Singh S. Sphingosine 1-Phosphate in malaria pathogenesis and its implication in therapeutic opportunities. Front Cell Infect Microbiol. 2020;10.

  57. Bode C, Sensken S-C, Peest U, Beutel G, Thol F, Levkau B, et al. Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphate. J Cell Biochem. 2010;109(6):1232–43.

    CAS  PubMed  Google Scholar 

  58. Urtz N, Gaertner F, von Bruehl M-L, Chandraratne S, Rahimi F, Zhang L, et al. Sphingosine 1-phosphate produced by sphingosine kinase 2 intrinsically controls platelet aggregation in vitro and in vivo. Circ Res. 2015;117(4):376–87.

    Article  CAS  PubMed  Google Scholar 

  59. Ancellin N, Colmont C, Su J, Li Q, Mittereder N, Chae S-S, et al. Extracellular export of sphingosine kinase-1 enzyme Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J Biol Chem. 2002;277(8):6667–75.

    Article  CAS  PubMed  Google Scholar 

  60. Venkataraman K, Thangada S, Michaud J, Oo ML, Ai Y, Lee Y-M, et al. Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient. Biochem J. 2006;397(3):461–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Vu TM, Ishizu A-N, Foo JC, Toh XR, Zhang F, Whee DM, et al. Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and platelets. Nature. 2017;550(7677):524–8.

    Article  CAS  PubMed  Google Scholar 

  62. Hisano Y, Kobayashi N, Yamaguchi A, Nishi T. Mouse SPNS2 functions as a sphingosine-1-phosphate transporter in vascular endothelial cells. PLoS ONE. 2012;7(6):e38941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Jonnalagadda D, Sunkara M, Morris AJ, Whiteheart SW. Granule-mediated release of sphingosine-1-phosphate by activated platelets. Biochim Biophys Acta BBA-Mol Cell Biol Lipids. 2014;1841(11):1581–9.

    CAS  Google Scholar 

  64. Cantalupo A, Zhang Y, Kothiya M, Galvani S, Obinata H, Bucci M, et al. Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure. Nat Med. 2015;21(9):1028–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. MacRitchie N, Volpert G, Al Washih M, Watson DG, Futerman AH, Kennedy S, et al. Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic model of pulmonary arterial hypertension. Cell Signal. 2016;28(8):946–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wilson PC, Fitzgibbon WR, Garrett SM, Jaffa AA, Luttrell LM, Brands MW, et al. Inhibition of sphingosine kinase 1 ameliorates angiotensin ii-induced hypertension and inhibits transmembrane calcium entry via store-operated calcium channel. Mol Endocrinol. 2015;29(6):896–908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Camm J, Hla T, Bakshi R, Brinkmann V. Cardiac and vascular effects of fingolimod: mechanistic basis and clinical implications. Am Heart J. 2014;168(5):632–44.

    Article  CAS  PubMed  Google Scholar 

  68. Cantalupo A, Gargiulo A, Dautaj E, Liu C, Zhang Y, Hla T, et al. S1PR1 (sphingosine-1-phosphate receptor 1) signaling regulates blood flow and pressure. Hypertension. 2017;70(2):426–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kurano M, Yatomi Y. Sphingosine 1-phosphate and atherosclerosis. J Atheroscler Thromb. 2017;RV17010.

  70. Tölle M, Levkau B, Keul P, Brinkmann V, Giebing G, Schönfelder G, et al. Immunomodulator FTY720 Induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3. Circ Res. 2005;96(8):913–20.

    Article  PubMed  Google Scholar 

  71. Salomone S, Soydan G, Ip PC-T, Hopson KMP, Waeber C. Vessel-specific role of sphingosine kinase 1 in the vasoconstriction of isolated basilar arteries. Pharmacol Res. 2010;62(6):465–74.

  72. Park S-J, Im D-S. Sphingosine 1-phosphate receptor modulators and drug discovery. Biomol Ther. 2017;25(1):80.

    Article  CAS  Google Scholar 

  73. Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, et al. HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal. 2015;8(389):ra79–ra79.

  74. Obinata H, Hla T. Sphingosine 1-phosphate and inflammation. Int Immunol. 2019;31(9):617–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Brizuela L, Rábano M, Gangoiti P, Narbona N, Macarulla JM, Trueba M, et al. Sphingosine-1-phosphate stimulates aldosterone secretion through a mechanism involving the PI3K/PKB and MEK/ERK 1/2 pathways. J Lipid Res. 2007;48(10):2264–74.

    Article  CAS  PubMed  Google Scholar 

  76. Chen J, Tang H, Sysol JR, Moreno-Vinasco L, Shioura KM, Chen T, et al. The sphingosine kinase 1/sphingosine-1-phosphate pathway in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2014;190(9):1032–43.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Meissner A, Miro F, Jimenez-Altayo F, Jurado A, Vila E, Planas AM. Sphingosine-1-phosphate signalling—a key player in the pathogenesis of Angiotensin II-induced hypertension. Cardiovasc Res. 2017;113(2):123–33.

    Article  CAS  PubMed  Google Scholar 

  78. Siedlinski M, Nosalski R, Szczepaniak P, Ludwig-Ga\lęzowska AH, Miko\lajczyk T, Filip M, et al. Vascular transcriptome profiling identifies Sphingosine kinase 1 as a modulator of angiotensin II-induced vascular dysfunction. Sci Rep. 2017;7:44131.

  79. Yang K, Jiang K, Xu Z, Song Y, Wang J. Targeting sphingosine kinase 1 for the treatment of pulmonary arterial hypertension. Future Med Chem. 2019;11(22):2939–53.

    Article  CAS  PubMed  Google Scholar 

  80. Pyne NJ, Pyne S. Sphingosine kinase 1: a potential therapeutic target in pulmonary arterial hypertension? Trends Mol Med. 2017;23(9):786–98.

    Article  CAS  PubMed  Google Scholar 

  81. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427(6972):355–60.

    Article  CAS  PubMed  Google Scholar 

  82. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, et al. Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction. J Exp Med. 2007;204(10):2449–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Itani HA, McMaster WG Jr, Saleh MA, Nazarewicz RR, Mikolajczyk TP, Kaszuba AM, et al. Activation of human T cells in hypertension: studies of humanized mice and hypertensive humans. Hypertension. 2016;68(1):123–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Schulze T, Golfier S, Tabeling C, Räbel K, Gräler MH, Witzenrath M, et al. Sphingosine-1-phospate receptor 4 (S1P4) deficiency profoundly affects dendritic cell function and TH17-cell differentiation in a murine model. FASEB J. 2011;25(11):4024–36.

    Article  CAS  PubMed  Google Scholar 

  85. van Hooren KW, Spijkers LJ, van Breevoort D, Fernandez-Borja M, Bierings R, van Buul JD, et al. Sphingosine-1-phosphate receptor 3 mediates sphingosine-1-phosphate induced release of weibel-palade bodies from endothelial cells. PLoS ONE. 2014;9(3):e91346.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Sanchez T, Skoura A, Wu MT, Casserly B, Harrington EO, Hla T. Induction of vascular permeability by the sphingosine-1-phosphate receptor–2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol. 2007;27(6):1312–8.

    Article  CAS  PubMed  Google Scholar 

  87. Li N, Zhang F. Implication of sphingosin-1-phosphate in cardiovascular regulation. Front Biosci Landmark Ed. 2016;21:1296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Sah RK, Saini M, Pati S, Singh S. Plasmodium falciparum growth is regulated by Sphingosine 1 phosphate produced by Host Erythrocyte Membrane Sphingosine kinase 1. bioRxiv. 2019;756502.

  89. Finney CA, Hawkes CA, Kain DC, Dhabangi A, Musoke C, Cserti-Gazdewich C, et al. S1P is associated with protection in human and experimental cerebral malaria. Mol Med. 2011;17(7):717–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Nacer A, Movila A, Sohet F, Girgis NM, Gundra UM, Daneman R, et al. Experimental cerebral malaria pathogenesis—hemodynamics at the blood brain barrier. PLoS Pathog. 2014;10(12):e1004528.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Nacer A, Movila A, Baer K, Mikolajczak SA, Kappe SH, Frevert U. Neuroimmunological blood brain barrier opening in experimental cerebral malaria. PLoS Pathog. 2012;8(10):e1002982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Punsawad C, Viriyavejakul P. Expression of sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 in malaria-associated acute lung injury/acute respiratory distress syndrome in a mouse model. PLoS ONE. 2019;14(9):e0222098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Birhanu M, Asres Y, Adissu W, Yemane T, Zemene E, Gedefaw L. Hematological parameters and hemozoin-containing leukocytes and their association with disease severity among malaria infected children: a cross-sectional study at Pawe General Hospital, Northwest Ethiopia. Interdiscip Perspect Infect Dis. 2017;2017.

  94. Dhangadamajhi G, Panigrahi S, Roy S, Tripathy S. Effect of Plasmodium falciparum infection on blood parameters and their association with clinical severity in adults of Odisha. India Acta Trop. 2019;190:1–8.

    Article  PubMed  Google Scholar 

  95. Zhang L, Orban M, Lorenz M, Barocke V, Braun D, Urtz N, et al. A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis. J Exp Med. 2012;209(12):2165–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. El Tahir A, Malhotra P, Chauhan VS. Uptake of proteins and degradation of human serum albumin by Plasmodium falciparum–infected human erythrocytes. Malar J. 2003;2(1):1–8.

    Article  Google Scholar 

  97. Visser BJ, Wieten RW, Nagel IM, Grobusch MP. Serum lipids and lipoproteins in malaria-a systematic review and meta-analysis. Malar J. 2013;12(1):1–16.

    Article  Google Scholar 

  98. Yeo TW, Weinberg JB, Lampah DA, Kenangalem E, Bush P, Chen Y, et al. Glycocalyx breakdown is associated with severe disease and fatal outcome in Plasmodium falciparum malaria. Clin Infect Dis. 2019;69(10):1712–20.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Cannon RE, Peart JC, Hawkins BT, Campos CR, Miller DS. Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain. Proc Natl Acad Sci. 2012;109(39):15930–5.

    Article  CAS  PubMed  Google Scholar 

  100. Oggungwan K, Glaharn S, Ampawong S, Krudsood S, Viriyavejakul P. FTY720 restores endothelial cell permeability induced by malaria sera. Sci Rep. 2018;8(1):1–6.

    Article  CAS  Google Scholar 

  101. Yanagida K, Liu CH, Faraco G, Galvani S, Smith HK, Burg N, et al. Size-selective opening of the blood–brain barrier by targeting endothelial sphingosine 1–phosphate receptor 1. Proc Natl Acad Sci. 2017;114(17):4531–6.

    Article  CAS  PubMed  Google Scholar 

  102. Hempel C, Sporring J, Kurtzhals JAL. Experimental cerebral malaria is associated with profound loss of both glycan and protein components of the endothelial glycocalyx. FASEB J. 2019;33(2):2058–71.

    Article  CAS  PubMed  Google Scholar 

  103. Oo ML, Chang S-H, Thangada S, Wu M-T, Rezaul K, Blaho V, et al. Engagement of S1P 1-degradative mechanisms leads to vascular leak in mice. J Clin Invest. 2011;121(6):2290–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Li P, Kondo T, Numaguchi Y, Kobayashi K, Aoki M, Inoue N, et al. Role of bradykinin, nitric oxide, and angiotensin II type 2 receptor in imidapril-induced angiogenesis. Hypertension. 2008;51(2):252–8.

    Article  CAS  PubMed  Google Scholar 

  105. Jensen AR, Adams Y, Hviid L. Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it. Immunol Rev. 2020;293(1):230–52.

    Article  CAS  PubMed  Google Scholar 

  106. Gillrie MR, Avril M, Brazier AJ, Davis SP, Stins MF, Smith JD, et al. Diverse functional outcomes of P lasmodium falciparum ligation of EPCR: potential implications for malarial pathogenesis. Cell Microbiol. 2015;17(12):1883–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Moussiliou A, Alao MJ, Denoeud-Ndam L, Tahar R, Ezimegnon S, Sagbo G, et al. High plasma levels of soluble endothelial protein C receptor are associated with increased mortality among children with cerebral malaria in Benin. J Infect Dis. 2015;211(9):1484–8.

    Article  CAS  PubMed  Google Scholar 

  108. Biancardi VC, Son SJ, Ahmadi S, Filosa JA, Stern JE. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood–brain barrier. Hypertension. 2014;63(3):572–9.

    Article  CAS  PubMed  Google Scholar 

  109. Beare NA, Glover SJ, Lewallen S, Taylor TE, Harding SP, Molyneux ME. Prevalence of raised intracranial pressure in cerebral malaria detected by optic nerve sheath ultrasound. Am J Trop Med Hyg. 2012;87(6):985–8.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Patil HV, others. Clinical profile and outcome of complicated Plasmodium falciparum malaria. Int J Med Public Health. 2012;2(1).

  111. Abdulazeez A, Ya’u M, Kurfi B, et al. Association of hypertension and activity of angiotensin converting enzyme in malaria patients attending Sheik Muhammad Jidda General Hospital, Kano State, Nigeria. Niger J Basic Clin Sci. 2017;14(2):121.

  112. Hoffmeister B, Valdez ADA. Hypertension is associated with an increased risk for severe imported falciparum malaria: a tertiary care hospital based observational study from Berlin, Germany. Malar J. 2019;18(1):410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Punsawad C, Viriyavejakul P. Reduction in serum sphingosine 1-phosphate concentration in malaria. PLoS ONE. 2017;12(6):e0180631.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Khan SJ, Abbass Y, Marwat MA. Thrombocytopenia as an indicator of malaria in adult population. Malar Res Treat. 2012;2012.

  115. Dondorp A. Clinical significance of sequestration in adults with severe malaria. Transfus Clin Biol. 2008;15(1–2):56–7.

    Article  CAS  PubMed  Google Scholar 

  116. Liles WC, Kain KC. Endothelial activation and dysfunction in the pathogenesis of microvascular obstruction in severe malaria—a viable target for therapeutic adjunctive intervention. J Infect Dis. 2014;210(1):163–4.

    Article  PubMed  Google Scholar 

  117. Hanson J, Lam SW, Mahanta KC, Pattnaik R, Alam S, Mohanty S, et al. Relative contributions of macrovascular and microvascular dysfunction to disease severity in falciparum malaria. J Infect Dis. 2012;206(4):571–9.

    Article  PubMed  Google Scholar 

  118. Graça L, Abreu IG, Santos AS, Graça L, Dias PF, Santos ML. Descriptive acute respiratory distress syndrome (ARDS) in adults with imported severe Plasmodium falciparum malaria: a 10 year-study in a Portuguese tertiary care hospital. PLoS ONE. 2020;15(7):e0235437.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Taylor WR, Hanson J, Turner GD, White NJ, Dondorp AM. Respiratory manifestations of malaria. Chest. 2012;142(2):492–505.

    Article  PubMed  Google Scholar 

  120. Viriyavejakul P, Punsawad C. Overexpression of sphingosine kinase-1 and sphingosine-1-phosphate receptor-3 in severe plasmodium falciparum malaria with pulmonary edema. BioMed Res Int. 2020;2020.

  121. Zhao J, Tan Y, Wang L, Su X, Shi Y. Serum sphingosine-1-phosphate levels and Sphingosine-1-Phosphate gene polymorphisms in acute respiratory distress syndrome: a multicenter prospective study. J Transl Med. 2020;18:1–11.

    Article  CAS  Google Scholar 

  122. Biollaz J, Brunner HR, Gavras I, Waeber B, Gavras H. Antihypertensive therapy with MK 4211: angiotensin II-renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982;4(6):966–72.

    Article  CAS  PubMed  Google Scholar 

  123. Klein N, Gembardt F, Supé S, Kaestle SM, Nickles H, Erfinanda L, et al. Angiotensin-(1–7) protects from experimental acute lung injury. Crit Care Med. 2013;41(11):e334–43.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

The present review is an upshot of the project proposal submitted to ICMR, Govt. of India for funding by both the authors. The funding agency has no role in designing, drafting, and decision to submit the review article for publication. We thankfully acknowledge the authors whose contributions have been cited and would like to apologize to those whose published articles could not be cited due to space constraints.

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  1. Department of Biotechnology, Maharaja Sriramchandra Bhanjadeo University, Takatpur, Baripada, Odisha, 75003, India

    Gunanidhi Dhangadamajhi

  2. Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India

    Shailja Singh

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  1. Gunanidhi Dhangadamajhi
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Dhangadamajhi, G., Singh, S. Malaria link of hypertension: a hidden syndicate of angiotensin II, bradykinin and sphingosine 1-phosphate. Human Cell 34, 734–744 (2021). https://doi.org/10.1007/s13577-021-00513-3

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