The role of MCP-1 and SDF-1 in impaired mobilization of endothelial progenitor cells from the bone marrow in coronary heart disease

It is relevant to study of angiogenesis mediators and the mobilization of early endothelial progenitor cells (EPС) from bone marrow into the blood in patients with coronary heart disease (CHD), suffering and not suffering from ischemic cardiomyopathy (ICMP).

СHD patients: 30 people with ICMP and 22 people without ICMP, 15 healthy donors. The content of early EPС (VEGFR2⁺CD34⁺CD14⁺) was determined in the blood and bone marrow by flow cytofluorometry, the concentration of MSP-1, SDF-1, VEGF-A – by multiplex analysis, of HIF-1α – by ELISA.

Тhe content of SDF-1 and HIF-1α in peripheral blood in patients with CHD without cardiomyopathy was higher than in healthy individuals (respectively 60.00 (50.00-80.00) pg/mL and 6.00 (5.00-6.20) ng/mL versus 30.00 (5.00-45.00) pg/mL, p = 0.049 and 4.60 (3.28-5.11) ng/mL, p = 0.049), with ICMP corresponded to the norm. Тhe concentration of SDF-1 in the bone marrow was higher, and the level of HIF-1α was less than their content in the bloodstream, regardless of the presence of ICMP (respectively 130.0 (90.0-170.0) pg/mL, p = 0.005 and 0.97 (0.80-1.11) ng/mL, p < 0.001). The level of MCP-1 in the blood varied within the normal range in patients with CHD of both study groups (190.0 (168.0-215.0) pg/mL), and in the bone marrow was higher only in patients with ICMP (406.5 (265.0-583.0) pg/mL, p = 0.028). Regardless of ICMP presence, the content of VEGF-A in the blood of patients with CHD corresponded to the norm (3.80 (1.00-6.50) pg/mL) and in myeloid tissue. The number of EPC was increased in the blood of patients with CHD without cardiomyopathy (0.70 (0.46-1.23) and 0.19 (0.13-0.32) %, p < 0.001) and corresponded to their number in the bone marrow. And in patients with ICMP, normal values of the indicator were recorded in the blood with the accumulation of EPC in myeloid tissue (0.57 (0.45-0.98) %, p = 0.019).

The development of ICMP is associated with the accumulation of early EPC in myeloid tissue due to their increased retention by an excess of MCP-1 in the bone marrow with weak involvement in the bloodstream due to the lack of a surplus of SDF-1 and HIF-1a in the blood.

1. Chumakova S.P., Urazova O.I., Shipulin V.M., Sukhodolo I.V., Stelmashenko A.I., Denisenko O.A., Andreev S.L., Demin M.S., Churina E.G. Production of angiogenesis mediators and the structure of the vascular wall in the heart in ischemic cardiomyopathy Acta Biomedica Scientifica = Acta Biomedica Scientifica, 2023. Vol. 8, no. 6. pp. 81-90. (In Russ.)

2. Calabrese E.J. Hormesis and endothelial progenitor cells. Dose Response, 2022, Vol. 20, no. 1, 15593258211068625. doi: 10.1177/15593258211068625

3. Chopra H., Hung M.K., Kwong D.L., Zhang C.F., Pow E.H.N. Insights into endothelial progenitor cells: origin, classification, potentials, and prospects. Stem Cells Int., 2018, Vol. 2018, 9847015. doi: 10.1155/2018/9847015.

4. Chumakova S.P., Urazova O.I., Shipulin V.M., Andreev S.L., Denisenko O.A., Gladkovskaya M.V., Litvinova L.S., Bubenchikov M.A. Role of angiopoietic coronary endothelial dysfunction in the pathogenesis of ischemic cardiomyopathy. Biomedicines. 2023, Vol. 11, no. 7, 1950. doi: 10.3390/biomedicines11071950.

5. Cowman S.J., Koh M.Y. Revisiting the HIF switch in the tumor and its immune microenvironment. Trends Cancer, 2022, Vol. 8, no. 1, pp. 28-42.

6. Del Buono M.G., Moroni F., Montone R.A., Azzalini L., Sanna T., Abbate A. Ischemic cardiomyopathy and heart failure after acute myocardial infarction. Curr. Cardiol. Rep., 2022, Vol. 24, no. 10, pp. 1505-1515.

7. Felker G.M., Shaw G.M., O’Connor C.M. A standardized definition of ischemic cardiomyopathy for use in clinical research. J. Am. Coll. Cardiol., 2002, Vol. 39, no. 2, pp. 208-210.

8. Jiang Q., Huang K., lu F., Deng S., Yang Z., Hu S. Modifying strategies for SDF-1/CXCR4 interaction during mesenchymal stem cell transplantation. Gen. Thorac. Cardiovasc. Surg., 2022, Vol. 70, no. 1, pp. 1-10.

9. Korbecki J., KojderK., Kapczuk P., Kupnicka P., Gawronska-Szklarz B., Gutowska I., Chlubek D., Baranowska-Bosiacka I. The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors – a review of literature. Int. J. Mol. Sci, 2021, Vol. 22, no. 2, 843. doi: 10.3390/ijms22020843.

10. Nagasawa T. CXCL12/SDF-1 andCXCR4. Front.Immunol.,2015,Vol.6,301. doi: 10.3389/fimmu.2015.00301.

11. Sato Т., Takeda N. The roles of HIF-1α signaling in cardiovascular diseases. J. Cardiol., 2023, Vol. 81, no. 2, pp. 202-208.

12. Shi С., Pamer E.G. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol., 2011, Vol. 11, no. 11, pp. 762-774.

13. Singh S., Anshita D., Ravichandiran V. MCP-1: Function, regulation, and involvement in disease. Int. Immunopharmacol., 2021, Vol. 101, Part B, 107598. doi: 10.1016/j.intimp.2021.107598.

14. Teh Y.C., Ding J.L., Ng L.G., Chong S.Z. Capturing the fantastic voyage of monocytes through time and space. Front. Immunol., 2019, Vol. 10, 834. doi: 10.3389/fimmu.2019.00834.

15. Zhong J., Rajagopalan S. Dipeptidyl peptidase-4 regulation of SDF-1/CXCR4 axis: implications for cardiovascular disease. Front. Immunol., 2015, Vol. 6, 477. doi: 10.3389/fimmu.2015.00477.

16. Zhou Y., Zhu X., Cui H., Shi J., Yuan G., Shi S., Hu Y. The Role of the VEGF family in coronary heartdisease. Front. Cardiovasc. Med., 2021, Vol. 8, 738325. doi: 10.3389/fcvm.2021.738325.