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Elevated plasma macrophage migration inhibitor factor is associated with hypertension and hypertensive left ventricular hypertrophy

Journal of Human Hypertension volume 37, pages 68–73 (2023)Cite this article

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Abstract

Previous studies have found that the macrophage migration inhibitor factor is associated with endothelial dysfunction and ventricular remodelling. The aim of this study was to explore the potential relationship between plasma macrophage migration inhibitor factor levels and hypertension and hypertensive left ventricular hypertrophy. A total of 308 participants (including 187 uncomplicated hypertensive patients and 121 healthy controls) were enroled from 2017 to 2019. The association between macrophage migration inhibitor factors and hypertension and hypertensive left ventricular hypertrophy was estimated with univariate and multivariate logistic regression models. Elevated macrophage migration inhibitor factor was associated with the development of hypertension (second tertile: adjusted OR, 2.27, 95% CI, 1.24–4.16, P = 0.008; third tertile: adjusted OR, 5.43, 95% CI, 2.75–10.71, P < 0.001; compared with the first tertile). In addition, we assessed the association between macrophage migration inhibitor factor and left ventricular hypertrophy in hypertensive patients (n = 187). Plasma macrophage migration inhibitor factor was significantly correlated with hypertensive left ventricular mass index (r = 0.580, P < 0.001). In patients with hypertension, an elevated macrophage migration inhibitor factor was significantly associated with hypertensive left ventricular hypertrophy (second tertile: adjusted OR, 3.20, 95% CI, 1.17–8.78, P = 0.024; third tertile: adjusted OR, 24.95, 95% CI, 8.72–71.41, P < 0.001; compared with the first tertile). Receiver operating characteristic analysis indicated that macrophage migration inhibitor factor had reasonable predictive accuracy for the development of hypertensive left ventricular hypertrophy (area under curve 0.84, 95% CI 0.78–0.90, P < 0.001). Our data indicated that elevated macrophage migration inhibitor factor is associated with hypertension and hypertensive left ventricular hypertrophy.

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Fig. 1: Plasma MIF level of hypertensive patients and correlations between MIF and blood pressure.
Fig. 2: Plasma MIF level of hypertensive LVH and correlations between MIF and LVMI.
Fig. 3: A receiver operating characteristic curve evaluating the predictive accuracy of MIF for the development of hypertensive LVH.

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References

  1. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the american college of cardiology/american heart association task force on clinical practice guidelines. Hypertension (Dallas, Tex: 1979). 2018;71:e13–e115.

    CAS  Google Scholar 

  2. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur heart J. 2018;39:3021–104.

    Article  Google Scholar 

  3. Stewart MH, Lavie CJ, Shah S, Englert J, Gilliland Y, Qamruddin S, et al. Prognostic implications of left ventricular hypertrophy. Prog Cardiovascular Dis. 2018;61:446–55.

    Article  Google Scholar 

  4. Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am heart J. 2001;141:334–41.

    Article  CAS  Google Scholar 

  5. Lavie CJ, Patel DA, Milani RV, Ventura HO, Shah S, Gilliland Y. Impact of echocardiographic left ventricular geometry on clinical prognosis. Prog Cardiovascular Dis. 2014;57:3–9.

    Article  Google Scholar 

  6. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003;3:791–800.

    Article  CAS  Google Scholar 

  7. White DA, Fang L, Chan W, Morand EF, Kiriazis H, Duffy SJ, et al. Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells. PloS One. 2013;8:e76206.

    Article  CAS  Google Scholar 

  8. Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007;13:587–96.

    Article  CAS  Google Scholar 

  9. Takahashi M, Nishihira J, Shimpo M, Mizue Y, Ueno S, Mano H, et al. Macrophage migration inhibitory factor as a redox-sensitive cytokine in cardiac myocytes. Cardiovascular Res. 2001;52:438–45.

    Article  CAS  Google Scholar 

  10. Zernecke A, Bernhagen J, Weber C. Macrophage migration inhibitory factor in cardiovascular disease. Circulation. 2008;117:1594–602.

    Article  CAS  Google Scholar 

  11. Asare Y, Schmitt M, Bernhagen J. The vascular biology of macrophage migration inhibitory factor (MIF). Expression and effects in inflammation, atherogenesis and angiogenesis. Thrombosis Haemost. 2013;109:391–8.

    Article  CAS  Google Scholar 

  12. Dayawansa NH, Gao XM, White DA, Dart AM, Du XJ. Role of MIF in myocardial ischaemia and infarction: insight from recent clinical and experimental findings. Clin Sci (Lond, Engl: 1979). 2014;127:149–61.

    Article  CAS  Google Scholar 

  13. Gao XM, Liu Y, White D, Su Y, Drew BG, Bruce CR, et al. Deletion of macrophage migration inhibitory factor protects the heart from severe ischemia-reperfusion injury: a predominant role of anti-inflammation. J Mol Cell Cardiol. 2011;50:991–9.

    Article  CAS  Google Scholar 

  14. Rassaf T, Weber C, Bernhagen J. Macrophage migration inhibitory factor in myocardial ischaemia/reperfusion injury. Cardiovascular Res. 2014;102:321–8.

    Article  CAS  Google Scholar 

  15. Chan W, White DA, Wang XY, Bai RF, Liu Y, Yu HY, et al. Macrophage migration inhibitory factor for the early prediction of infarct size. J Am Heart Assoc. 2013;2:e000226.

    Article  Google Scholar 

  16. Zhou B, Ren C, Zu L, Zheng L, Guo L, Gao W. Elevated plasma migration inhibitory factor in hypertension-hyperlipidemia patients correlates with impaired endothelial function. Medicine. 2016;95:e5207.

    Article  CAS  Google Scholar 

  17. Li X, Xue YM, Guo HM, Deng CY, Peng DW, Yang H, et al. High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines. Life Sci. 2020;242:117209.

    Article  CAS  Google Scholar 

  18. Liu LS. 2010 Chinese guidelines for the management of hypertension. Zhonghua xin xue guan bing za zhi. 2011;39:579–615.

    Google Scholar 

  19. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr: Off Publ Am Soc Echocardiogr. 2005;18:1440–63.

    Article  Google Scholar 

  20. Zhang T, Li S, Bazzano L, He J, Whelton P, Chen W. Trajectories of childhood blood pressure and adult left ventricular hypertrophy: the bogalusa heart study. Hypertension (Dallas, Tex: 1979). 2018;72:93–101.

    Article  CAS  Google Scholar 

  21. Slade T, Mewton L, O’Dean S, Tibbetts J, Clay P, Isik A, et al. DSM-5 and ICD-11 alcohol use disorder criteria in young adult regular drinkers: Lifetime prevalence and age of onset. Drug Alcohol Depend. 2021;229:109184. Pt B

    Article  Google Scholar 

  22. Gao Y, Chen G, Tian H, Lin L, Lu J, Weng J, et al. Prevalence of hypertension in china: a cross-sectional study. PloS One. 2013;8:e65938.

    Article  CAS  Google Scholar 

  23. Sarzani R, Salvi F, Dessì-Fulgheri P, Rappelli A. Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. J Hypertension. 2008;26:831–43.

    Article  CAS  Google Scholar 

  24. Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. Hypertension. Nat Rev Dis Prim. 2018;4:18014.

    Article  Google Scholar 

  25. De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury. Arteriosclerosis, Thrombosis, Vasc Biol. 2005;25:2106–13.

    Article  Google Scholar 

  26. Garcia JA, Incerpi EK. Factors and mechanisms involved in left ventricular hypertrophy and the anti-hypertrophic role of nitric oxide. Arquivos Brasileiros de Cardiologia. 2008;90:409–16.

    Google Scholar 

  27. Yildiz M, Oktay AA, Stewart MH, Milani RV, Ventura HO, Lavie CJ. Left ventricular hypertrophy and hypertension. Prog Cardiovascular Dis. 2020;63:10–21.

    Article  Google Scholar 

  28. Le Hiress M, Tu L, Ricard N, Phan C, Thuillet R, Fadel E, et al. Proinflammatory signature of the dysfunctional endothelium in pulmonary hypertension. role of the macrophage migration inhibitory Factor/CD74 Complex. Am J Respiratory Crit Care Med. 2015;192:983–97.

    Article  Google Scholar 

  29. Le Hiress M, Akagah B, Bernadat G, Tu L, Thuillet R, Huertas A, et al. Design, synthesis, and biological activity of new N-(Phenylmethyl)-benzoxazol-2-thiones as macrophage migration inhibitory factor (MIF) antagonists: efficacies in experimental pulmonary hypertension. J Medicinal Chem. 2018;61:2725–36.

    Article  Google Scholar 

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Author notes

  1. These authors contributed equally: Ling Zhu, Shasha Chen.

Authors and Affiliations

  1. Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, 710000, China

    Ling Zhu, Qianwei Cui, Minzhi Ma, Zhongwei Liu, Yujie Xing, Yong Zhang & Junkui Wang

  2. Department of Cardiology, The Third Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, China

    Ling Zhu

  3. Department of Ultrasound, The School Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, China

    Shasha Chen

  4. Department of Pediatric Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, 710000, China

    Na Liu

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Zhu, L., Chen, S., Liu, N. et al. Elevated plasma macrophage migration inhibitor factor is associated with hypertension and hypertensive left ventricular hypertrophy. J Hum Hypertens 37, 68–73 (2023). https://doi.org/10.1038/s41371-022-00657-1

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