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Original research
Strengthening effects of bone marrow mononuclear cells with intensive atorvastatin in acute myocardial infarction
  1. Yue-Jin Yang1,
  2. Hai-Yan Qian1,
  3. Lei Song1,
  4. Yong-Jian Geng2,
  5. Run-lin Gao1,
  6. Na Li3,
  7. Hong Wang4,
  8. Xia-Qiu Tian4,
  9. Ji Huang5,
  10. Pei-Sen Huang1,
  11. Jun Xu1,
  12. Rui Shen6,
  13. Min-Jie Lu7,
  14. Shi-Hua Zhao7,
  15. Wei-Chun Wu8,
  16. Yuan Wu1,
  17. Jun Zhang1,
  18. Jie Qian1,
  19. Jun-Yan Xu1 and
  20. Yu-Yan Xiong1
  1. 1Department of Cardiology, Center for Coronary Heart Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  2. 2The Center for Cardiovascular Biology and Atherosclerosis, Department of Internal Medicine, University of Texas McGovern School of Medicine at Houston, Houston, Texas, USA
  3. 3Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
  4. 4Center for Cardiac Critical Care, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
  5. 5Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
  6. 6Department of Nuclear Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  7. 7Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  8. 8Department of Echocardiography, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  1. Correspondence to Yue-Jin Yang; yangyjfw{at}126.com

Abstract

Objective To test whether intensive atorvastatin (ATV) increases the efficacy of transplantation with autologous bone marrow mononuclear cells (MNCs) in patients suffering from anterior ST-elevated myocardial infarction (STEMI).

Methods This clinical trial was under a 2×2 factorial design, enrolling 100 STEMI patients, randomly into four groups of regular (RA) or intensive ATV (IA) with MNCs or placebo. The primary endpoint was the change of left ventricular ejection fraction (LVEF) at 1-year follow-up from baseline, primarily assessed by MRI. The secondary endpoints included other parameters of cardiac function, remodelling and regeneration determined by MRI, echocardiography, positron emission tomography (PET) and biomarkers.

Results All the STEMI patients with transplantation of MNCs showed significantly increased LVEF change values than those with placebo (p=0.01) with only in the IA+MNCs patients group demonstrating significantly elevation of LVEF than in the IA+placebo group (+12.6% (95%CI 10.4 to 19.3) vs +5.0% (95%CI 4.0 to 10.0), p=0.001), pointing to a better synergy between ATV and MNCs (p=0.019). PET analysis revealed significantly increased viable areas of myocardium (p=0.015), while the scar sizes (p=0.026) and blood aminoterminal pro-B-type natriuretic peptide (p<0.034) reduced. All these above benefits of MNCs were also attributed to IA+MNCs instead of RA+MNCs group of patients with STEMI.

Conclusions Intensive ATV treatment augments the therapeutic efficacy of MNCs in patients with anterior STEMI at the convalescent stage. The treatment with the protocol of intensive ATV and MNC combination offers a clinically essential approach for myocardial infarction.

Trial registration number NCT00979758.

  • acute coronary syndrome
  • myocardial perfusion
  • statins
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Footnotes

  • Y-JY and H-YQ contributed equally.

  • Contributors The coauthors including Y-JY, Y-JG, H-YQ and R-LG contributed to the planning, the coauthors including LS, NL, HW, X-QT, JH, P-SH, JX, RS, M-JL, S-HZ, W-CW and JQ contributed to the conduct and the coauthors including YW, JZ, J-YX and Y-YX contributed to the reporting of the work in the article. Among the above coauthors, professors Y-JY and H-YQ are responsible for the overall contents as guarantors. We did not include any figure or table from another publication.

  • Funding Y-JY was supported by grants from CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-12 M-1-009), National Basic Research Program (973 Program) in China (no: 2012CB518602, Ministry of Science and Technology), National High Technology Research and Development Program (863 Program) in China (no: 2013AA020101, Ministry of Science and Technology), National Natural Science Foundation of China (no: 81170129), Research Fund of Capital Medical Development (no: 2007–2018) and China Health and Medical Development Foundation (2008-zhfj2, 2011-zhfj1, 2015-zhfj2). H-YQ was supported by grants from the Clinical and Translational Medicine Research Foundation of Chinese Academy of Medical Sciences (2019XK320061), and National Natural Science Foundation of China (nos: 81000091, 81670337).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The institutional review boards of Fuwai Cardiovascular Hospital of the Chinese Academy of Medical Sciences reviewed and approved the study protocol.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The related data can be requested from the co-author Professor H-YQ via email at ahqhy712@163.com.

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