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Improvement of physical activity significantly reduced serum hepatocyte growth factor levels in a general population: 10 year prospective study

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Abstract

Hepatocyte growth factor (HGF) is an adipocytokine elevated in obese subjects. We have previously reported that serum HGF levels were significantly associated with insulin resistance or components of the metabolic syndrome. However, it has been unknown how physical activity (PA) affects HGF levels after a long-term follow-up. Our aim was to clarify the association between PA changes and HGF levels as well as cerebro-cardiovascular disease (CVD) development, during a 10 year follow-up period in a Japanese general population. Of 1320 subjects who received a health check-up examination in Tanushimaru town in 1999, 903 subjects (341 males and 562 females), who received the examination both in 1999 and 2009 were enrolled. We evaluated their PA levels by Baecke questionnaire in 1999 and by a simple questionnaire in 2009. We measured the HGF levels by ELISA method in 1999 and 2009. We divided the subjects into four PA groups, stable low PA, increased PA, decreased PA, and stable high PA. Using these questionnaires, we compared their PA and HGF levels after an interval of 10 years. A significant inverse association was found between PA changes and HGF levels at 10 years, after adjustment for age and sex. The HGF levels of the increased PA group were significantly lower than stable low PA (p = 0.038), and the increased PA group showed reduced CVD development compared to the stable low PA group after adjustment for age and sex (p = 0.012). Our data demonstrated that improvement of PA levels was associated with reduced HGF levels and CVD development.

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References

  1. Nakamura T, Nawa K, Ichihara A (1984) Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun 122:1450–1459

    Article  CAS  PubMed  Google Scholar 

  2. Nakamura T, Teramoto H, Ichihara A (1986) Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci USA 83:6489–6493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hiratsuka A, Adachi H, Fujiura Y, Yamagishi S, Hirai Y, Enomoto M, Satoh A, Hino A, Furuki K, Imaizumi T (2005) Strong association between serum hepatocyte growth factor and metabolic syndrome. J Clin Endocrinol Metab 90:2927–2931

    Article  CAS  PubMed  Google Scholar 

  4. Tsukagawa E, Adachi H, Hirai Y, Enomoto M, Fukami A, Ogata K, Kasahara A, Yokoi K, Imaizumi T (2013) Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10 year prospective study. Clin Endocrinol 79:43–48

    Article  CAS  Google Scholar 

  5. Haufe S, Kerling A, Protte G, Bayerle P, Stenner HT, Rolff S, Sundermeier T, Kück M, Ensslen R, Nachbar L, Lauenstein D, Böthig D, Bara C, Hanke AA, Terkamp C, Stiesch M, Hilfiker-Kleiner D, Haverich A, Tegtbur U (2019) Telemonitoring-supported exercise training, metabolic syndrome severity, and work ability in company employees: a randomized controlled trial. Lancet Public Health 4:e343-352

    Article  PubMed  Google Scholar 

  6. Myers J, Kokkinos P, Nyelin E (2019) Physical activity, cardiorespiratory fitness, and the metabolic syndrome. Nutrients 11:1652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Roberts CK, Hevener AL, Barnard RJ (2013) Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. Compre Physiol 3:1–58

    Google Scholar 

  8. Henriksen EJ (2002) Invited review: effects of acute exercise and exercise training on insulin resistance. J Appl Physiol 93:788–796

    Article  CAS  PubMed  Google Scholar 

  9. Adachi H, Hirai Y, Sasaki S, Enomoto M, Fukami A, Kumagai E, Esaki E, Imaizumi T (2011) Trends in dietary intakes and serum cholesterol levels over 50 years in tanushimaru in Japanese men. Food Nutr Sci 2:476–481

    CAS  Google Scholar 

  10. Hino A, Adachi H, Toyomasu K, Yoshida N, Enomoto M, Hiratsuka A, Hirai Y, Satoh A, Imaizumi T (2004) Very long chain N-3 fatty acids intake and carotid atherosclerosis: an epidemiological study evaluated by ultrasonography. Atherosclerosis 176:145–149

    Article  CAS  PubMed  Google Scholar 

  11. Baecke JA, Burema J, Frijters JE (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 36:936–942

    Article  CAS  PubMed  Google Scholar 

  12. Sakaue A, Adachi H, Enomoto M, Fukami A, Kumagai E, Nakamura S, Nohara Y, Kono S, Nakao E, Morikawa N, Tsuru T, Hamamura H, Yoshida N, Fukumoto Y (2020) Association between physical activity, occupational sitting time and mortality in a general population: An 18 year prospective survey in Tanushimaru, Japan. Eur J Prev Cardiol 27:758–766

    Article  PubMed  Google Scholar 

  13. Oyeyemi AL, Moss SJ, Monyeki MA, Kruger HS (2016) Measurement of physical activity in urban and rural South African adults: a comparison of two self-report methods. BMC Public Health 16:1004

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yamada A, Matsumoto K, Iwanari H, Sekiguchi K, Kawata S, Matsuzawa Y, Nakamura T (1995) Rapid and sensitive enzyme-linked immunosorbent assay for measurement of HGF in rat and human tissues. Biomed Res 16:105–114

    Article  CAS  Google Scholar 

  15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  16. Ura N, Saitoh S, Shimamoto K (2007) Clinical diagnosis of metabolic syndrome 1: metabolic syndrome and insulin resistance. Intern Med 46:1283–1284

    Article  PubMed  Google Scholar 

  17. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992

    Article  CAS  PubMed  Google Scholar 

  18. Florido R, Kwak L, Lazo M, Nambi V, Ahmed HM, Hegde SM, Gerstenblith G, Blumenthal RS, Ballantyne CM, Selvin E, Folsom AR, Coresh J, Ndumele CE (2018) Six-year changes in physical activity and the risk of incident heart failure: aric study. Circulation 137:2142–2151

    Article  PubMed  PubMed Central  Google Scholar 

  19. Decker PA, Larson NB, Bell EJ, Pankow JS, Hanson NQ, Wassel CL, Tsai MY, Bielinski SJ (2019) Increased hepatocyte growth factor levels over 2 years are associated with coronary heart disease: the multi-ethnic study of atherosclerosis (MESA). Am Heart J 213:30–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lamblin N, Susen S, Dagorn J, Mouquet F, Jude B, Van Belle E, Bauters C, de Groote P (2005) Prognostic significance of circulating levels of angiogenic cytokines in patients with congestive heart failure. Am Heart J 150:137–143

    Article  CAS  PubMed  Google Scholar 

  21. Bell EJ, Larson NB, Decker PA, Pankow JS, Tsai MY, Hanson NQ, Wassel CL, Longstreth WT Jr, Bielinski SJ (2016) Hepatocyte growth factor is positively associated with risk of stroke: the MESA (multi-ethnic study of atherosclerosis). Stroke 47:2689–2694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bell EJ, Decker PA, Tsai MY, Pankow JS, Hanson NQ, Wassel CL, Larson NB, Cohoon KP, Budoff MJ, Polak JF, Stein JH, Bielinski SJ (2018) Hepatocyte growth factor is associated with progression of atherosclerosis: the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis 272:162–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Osibogun O, Ogunmoroti O, Ferraro RA, Ndumele CE, Burke GL, Larson NB, Bielinski SJ, Michos ED (2022) Favorable cardiovascular health is associated with lower hepatocyte growth factor levels in the multi-ethnic study of atherosclerosis. Front Cardiovasc Med 8:760281

    Article  PubMed  PubMed Central  Google Scholar 

  24. Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA (1991) Production of transforming growth factor beta 1 during repair of arterial injury. J Clin Invest 88:904–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nikol S, Isner JM, Pickering JG, Kearney M, Leclerc G, Weir L (1992) Expression of transforming growth factor-beta 1 is increased in human vascular restenosis lesions. J Clin Invest 90:1582–1592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nakano N, Morishita R, Moriguchi A, Nakamura Y, Hayashi SI, Aoki M, Kida I, Matsumoto K, Nakamura T, Higaki J, Ogihara T (1998) Negative regulation of local hepatocyte growth factor expression by angiotensin II and transforming growth factor-beta in blood vessels: potential role of HGF in cardiovascular disease. Hypertension 32:444–451

    Article  CAS  PubMed  Google Scholar 

  27. Florido R, Zhao DI, Ndumele CE, Bluemke DA, Heckbert SR, Allison MA, Ambale-Venkatesh B, Liu CY, Lima J, Michos ED (2019) Change in physical activity and cardiac structure over 10 years: the multi-ethnic study of atherosclerosis. Med Sci Sports Exerc 51:2033–2040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Castro-Diehl C, Song RJ, Sawyer DB, Wollert KC, Mitchell GF, Cheng S, Vasan RS, Xanthakis V (2021) Circulating growth factors and cardiac remodeling in the community: the Framingham heart study. Int J Cardiol 329:217–224

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lamblin N, Bauters A, Fertin M, de Groote P, Pinet F, Bauters C (2011) Circulating levels of hepatocyte growth factor and left ventricular remodeling after acute myocardial infarction (from the REVE-2 study). Eur J Heart Fail 13:1314–1322

    Article  CAS  PubMed  Google Scholar 

  30. Kuznetsova T, Haddad F, Knez J, Rosenberg-Hasson Y, Sung J, Cauwenberghs N, Thijs L, Karakikes I, Maecker H, Mahaffey KW, Wu JC, Staessen JA (2015) Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction. J Am Soc Hypertens 9:975–984

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

AS was primary investigator and performed this examination. HA, ME, AF, YN, NM, MY, and HS. planned and performed this study. KM performed the statistical analysis. YF designed this study and he is a head of the department supervisor. All the authors read and approved the final manuscript. We are grateful to the members of the Japan Medical Association of Ukiha, the elected officials and residents of Tanushimaru, and the team of cooperating physicians for their help in performing the health examinations. This study was supported in part by the Kimura Memorial Heart Foundation (Fukuoka, Japan).

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Correspondence to Hisashi Adachi.

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A. Sakaue, H. Adachi, M. Enomoto, A. Fukami, Y. Nohara, N. Morikawa, M. Yamamoto, H. Sato, K. Murotani, and Y. Fukumoto declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

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Sakaue, A., Adachi, H., Enomoto, M. et al. Improvement of physical activity significantly reduced serum hepatocyte growth factor levels in a general population: 10 year prospective study. Heart Vessels 38, 588–598 (2023). https://doi.org/10.1007/s00380-022-02198-6

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  • DOI: https://doi.org/10.1007/s00380-022-02198-6

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