Association Between Increased Expression Levels of SDF-1 and CXCR4 on the Platelets of Patients With Coronary Artery Disease and Low LVEF

Document Type : Original Article


1 Department of Laboratory Sciences, School of Allied Medical Sciences, Alborz University of Medical Sciences, Karaj, IR Iran.

2 Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

3 Department of Cardiology, Taleghani general Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

4 HSC Research Center- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

5 Physiotherapy Research Center, Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.


Background: Since coronary artery disease (CAD) is one of the leading causes of death globally, identifying new risk factors can augment risk assessment. This study aimed to investigate the surface expression of stromal cell-derived factor-1 (SDF-1), CXCR4, and CXCR7 on the platelets of CAD patients and to determine whether there is a correlation between their expressions and left ventricular ejection fraction (LVEF).
Methods: Sixty CAD patients and 60 healthy volunteers as normal controls were studied. The mean fluorescence intensity (MFI) of SDF-1 and its receptor expression was evaluated by flow cytometry. Biochemical markers and platelet parameters were investigated with an AutoAnalyzer and a cell counter, respectively.
Results: The platelets of the CAD group expressed SDF-1 and CXCR4 significantly more than those of the control group (MFI=1112±304 vs 943±131; P=0.042 and MFI=23372±6804 vs 20634±3482; P=0.033, respectively). Nevertheless, no significant difference was found in the platelet expression of CXCR7 between the CAD and control groups (MFI=35256±8706 vs 25053±7270; P=0.061). Notably, increased expression levels of SDF-1 and CXCR4 were associated with decreased LVEF (r= −0.388, P=0.003 and r= −0.431, P=0.001).
Conclusions: Our findings demonstrated that the overexpression of SDF-1 and CXCR4 on platelets could be considered a promising candidate indicating that asymptomatic patients with decreased LVEF may be at the risk of CAD. (Iranian Heart Journal 2022; 23(1): 42-53)


  1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS medicine. 2006;3(11):e442.
  2. Members WG, Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, et al. Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113(6):e85-e151.
  3. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129(3):399-410.
  4. Association AH. Heart Disease and Stroke Statistics 2017 At-a-Glance. on-line at: http://www heart org/idc/groups/ahamahpublic/@ wcm/@ sop/@ smd/documents/downloadable/ucm_491265 pdf. 2017.
  5. Hajar R. Risk factors for coronary artery disease: Historical perspectives. Heart views: the official journal of the Gulf Heart Association. 2017;18(3):109.
  6. Akhabue E, Thiboutot J, Cheng J-w, Lerakis S, Vittorio TJ, Christodoulidis G, et al. New and emerging risk factors for coronary heart disease. The American journal of the medical sciences. 2014;347(2):151-8.
  7. Aukrust Pl, Halvorsen B, Yndestad A, Ueland T, Øie E, Otterdal K, et al. Chemokines and cardiovascular risk. Arteriosclerosis, thrombosis, and vascular biology. 2008;28(11):1909-19.
  8. Laflamme MA, Murry CE. Heart regeneration. Nature. 2011;473(7347):326.
  9. van der Vorst EP, Döring Y, Weber C. MIF and CXCL12 in cardiovascular diseases: functional differences and similarities. Frontiers in immunology. 2015;6:373.
  10. Chatterjee M, Gawaz M. Platelet‐derived CXCL 12 (SDF‐1α): basic mechanisms and clinical implications. Journal of Thrombosis and Haemostasis. 2013;11(11):1954-67.
  11. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. Stromal cell–derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation. 2004;110(21):3300-5.
  12. Geisler T, Fekecs L, Wurster T, Chiribiri A, Schuster A, Nagel E, et al. Association of platelet-SDF-1 with hemodynamic function and infarct size using cardiac MR in patients with AMI. European journal of radiology. 2012;81(4):e486-e90.
  13. Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. Journal of Biological Chemistry. 2005.
  14. Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clinical cancer research. 2010:1078-0432. CCR-09-2329.
  15. Yamaguchi J-i, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, et al. Stromal cell–derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation. 2003;107(9):1322-8.
  16. Naumann U, Cameroni E, Pruenster M, Mahabaleshwar H, Raz E, Zerwes H-G, et al. CXCR7 functions as a scavenger for CXCL12 and CXCL11. PloS one. 2010;5(2):e9175.
  17. Melo RdCC, Ferro KPV, Duarte AdSS, Saad STO. CXCR7 participates in CXCL12-mediated migration and homing of leukemic and normal hematopoietic cells. Stem cell research & therapy. 2018;9(1):34.
  18. D'Souza M, Sarkisian L, Saaby L, Poulsen TS, Gerke O, Larsen TB, et al. Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays. The American journal of medicine. 2015;128(8):852-60.
  19. Bax JJ, Baumgartner H, Ceconi C, Dean V, Fagard R, Funck-Brentano C, et al. Third universal definition of myocardial infarction. Journal of the American College of Cardiology. 2012;60(16):1581-98.
  20. Rath D, Chatterjee M, Borst O, Müller K, Stellos K, Mack AF, et al. Expression of stromal cell-derived factor-1 receptors CXCR4 and CXCR7 on circulating platelets of patients with acute coronary syndrome and association with left ventricular functional recovery. European heart journal. 2013;35(6):386-94.
  21. Kajstura J, Urbanek K, Rota M, Bearzi C, Hosoda T, Bolli R, et al. Cardiac stem cells and myocardial disease. Journal of molecular and cellular cardiology. 2008;45(4):505-13.
  22. Stellos K, Bigalke B, Langer H, Geisler T, Schad A, Kögel A, et al. Expression of stromal-cell-derived factor-1 on circulating platelets is increased in patients with acute coronary syndrome and correlates with the number of CD34+ progenitor cells. European heart journal. 2008;30(5):584-93.
  23. Mehrpouri M, Bashash D, Mohammadi MH, Gheydari ME, Satlsar ES, Hamidpour M. Co-culture of Platelets with Monocytes Induced M2 Macrophage Polarization and Formation of Foam Cells: Shedding Light on the Crucial Role of Platelets in Monocyte Differentiation. Turkish Journal of Hematology. 2019;36(2):97.
  24. Derakhshan R, Arababadi MK, Ahmadi Z, Karimabad MN, Salehabadi VA, Abedinzadeh M, et al. Increased circulating levels of SDF-1 (CXCL12) in type 2 diabetic patients are correlated to disease state but are unrelated to polymorphism of the SDF-1β gene in the Iranian population. Inflammation. 2012;35(3):900-4.
  25. Li S-L, Lin W, Zhang Y, Zheng Z-C, Liu L-J, Fu H, et al. Stromal Cell-Derived Factor-1α as a Novel Biomarker for Hyperlipidemia. The Tohoku journal of experimental medicine. 2012;228(4):355-63.
  26. Ribeiro V, Bosquetti B, Gonçalves SM, Bucharles SGE, Rempel L, Maciel RAP, et al. Uremic serum inhibits in vitro expression of chemokine SDF-1: impact of uremic toxicity on endothelial injury. Jornal Brasileiro de Nefrologia. 2014;36(2):123-31.
  27. Chu H, Chen W-L, Huang C-C, Chang H-Y, Kuo H-Y, Gau C-M, et al. Diagnostic performance of mean platelet volume for patients with acute coronary syndrome visiting an emergency department with acute chest pain: the Chinese scenario. Emergency Medicine Journal. 2010:emj. 2010.093096.
  28. Ihara A, Kawamoto T, Matsumoto K, Shouno S, Hirahara C, Morimoto T, et al. Relationship between platelet indexes and coronary angiographic findings in patients with ischemic heart disease. Pathophysiology of haemostasis and thrombosis. 2006;35(5):376-9.
  29. Islam M, Siddiqui N, Begum M, Bhuiyan A, Rahman M, Ahammed S. Diagnostic Importance of Platelet in Patients with Acute Coronary Syndrome Admitted in Mymensingh Medical College Hospital. Mymensingh medical journal: MMJ. 2017;26(1):61-7.
  30. Lippi G, Filippozzi L, Salvagno GL, Montagnana M, Franchini M, Guidi GC, et al. Increased mean platelet volume in patients with acute coronary syndromes. Archives of pathology & laboratory medicine. 2009;133(9):1441-3.
  31. Rodrigues B, França HH, Maiello JR, Romanini S, Pasuld F, Nunes E, et al. Mean Platelet Volume (MPV) Analysis In Patients with Coronary Arterial Disease. Am Soc Hematology; 2010.
  32. Majumder B, Jain H, Chatterjee S, Das TK. Study of platelet count and platelet volume indices in the spectrum of coronary artery diseases and its clinicopathological correlation. Nigerian Journal of Cardiology. 2018;15(1):63.
  33. Freixa X, Chan J, Bonan R, Ibrahim R, Lamarche Y, Demers P, et al. Impact of coronary artery disease on left ventricular ejection fraction recovery following transcatheter aortic valve implantation. Catheterization and Cardiovascular Interventions. 2015;85(3):450-8.
  34. Squeri A, Gaibazzi N, Reverberi C, Caracciolo MM, Ardissino D, Gherli T. Ejection fraction change and coronary artery disease severity: a vasodilator contrast stress-echocardiography study. Journal of the American Society of Echocardiography. 2012;25(4):454-9.
  35. Yun S-H, Sim E-H, Goh R-Y, Park J-I, Han J-Y. Platelet activation: the mechanisms and potential biomarkers. BioMed research international. 2016;2016.