Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy
Abstract
:1. Introduction
2. Methods
2.1. Clinical Characteristics of CHD Patients
2.2. Research Material
2.3. Immunophenotyping of EPCs and EDCs Using Flow Cytometry
2.4. Measurement of the Concentration of Mediators in the Blood
2.5. Statistical Analysis of Data
3. Results
3.1. Evaluation of the Balance of Destructive and Reparative Processes in the Coronary Vessels and in the Systemic Circulation in CHD Patients with and without ICMP
3.2. The Content of Vasomotor Endothelial Dysfunction Mediators in the Heart and the HIF-Dependent Tissue Response Imbalance to Hypoxia in CHD Patients, Suffering and Not Suffering from ICMP
3.3. Balance of the Mediators of Angiopoietic Endothelial Dysfunction in the Heart and Systemic Circulation of Patients with Coronary Heart Disease, Suffering and Not Suffering from ICMP
3.4. Interrelationship in the Balance between the Reparative and Destructive Processes in the Endothelium and HIFs-Dependent Mediator Response to Hypoxia with Factors of Angiopoietic and Vasomotor Forms of Endothelial Dysfunction in the Coronary and Systemic Circulation of CHD Patients, Suffering and Not Suffering from ICMP
4. Discussion
4.1. The Development of ICMP Is Not Accompanied by a More Pronounced Vasomotor Endothelial Dysfunction of the Coronary Vessels Compared to CHD without Cardiomyopathy
4.2. The Coronary Vessels’ Endothelium Desquamation in ICMP Is Increased, Which Is Not Accompanied by the EPC Mobilization from the Bone Marrow Due to the Absence of the Excess of SDF-1 and MCP-1 Chemoattractants in the Blood
4.3. HIF-1 and HIF-2 Imbalance in ICMP Does Not Affect VEGF-A Production but Reduces PDGF Production and VEGF-B Consumption in the Myocardium, Disrupting Vessels’ Early Stabilization
4.4. In ICMP, a High Content of Ang-2 and MMP-9 without an Adequate Increase in VEGF-A in the Myocardium Has a Destructive Effect on the Vessels Associated with Galectin-3 Hyperproduction in the Heart
4.5. The ICMP Pathogenesis Is Associated with Angiopoietic Endothelial Dysfunction, which Involves an Uncoordinated Mediator Response to Ischemia and Atherogenesis
5. Conclusions
6. Research Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Parameters | CHD Patients without ICMP | CHD Patients with ICMP | p |
---|---|---|---|
Number of patients: | 40 | 47 | - |
male | 33 (82.50%) | 42(89.36%) | 0.540 |
female | 7 (17.50%) | 5(10.64%) | 0.540 |
Age, years | 64.5 [58.5; 68.0] | 61.0 [57.0; 64.5] | 0.123 |
CHD duration, years | 5.00 [2.50; 9.00] | 3.50 [1.00; 6.50] | 0.264 |
Body mass index, kg/m2 | 29.48 [26.33; 32.51] | 28.07 [26.69; 31.18] | 0.650 |
Functional class of angina | |||
II | 7 (17.50%) | 11 (23.40%) | 0.680 |
of effort | |||
III | 29 (72.50%) | 31 (65.96%) | 0.671 |
IV | 4 (10.00%) | 5 (10.64%) | 0.798 |
Heart failure I NYHA | 4 (10.00%) | 3 (6.38%) | 0.824 |
Heart failure II NYHA | 16 (40.00%) | 28 (59.57%) | 0.109 |
Heart failure III NYHA | 20 (50.00%) | 16 (34.04%) | 0.198 |
LV ejection fraction, % | 59.25 [50.00; 67.50] | 31.50 [23.25; 36.50] | <0.001 |
Eventual systolic index of LV, mL/m2 | 52.90 [50.20; 56.90] | 75.30 [64.30; 82.30] | 0.004 |
LV myocardium mass, g | 184.0 [140.5; 214.5] | 233.0 [221.7; 266.2] | <0.001 |
Statin therapy | 34 (85.00%) | 39 (82.98%) | 0.971 |
Hypertensive disease stage III | 33 (82.50%) | 32 (68.09%) | 0.196 |
Type 2 diabetes mellitus | 13 (32.50%) | 4 (8.51%) | 0.011 |
Gastric and/or duodenal ulcer | 9 (22.50%) | 5 (10.64%) | 0.227 |
Diseases of liver and biliary tract | 5 (12.50%) | 3 (6.38%) | 0.541 |
Chronic kidney disease | 9 (22.50%) | 15 (31.91%) | 0.460 |
Pulmonary diseases | 6 (15.00%) | 8 (17.02%) | 0.971 |
Blood Parameters | Healthy Donors | CHD Patients without ICMP | CHD Patients with ICMP |
---|---|---|---|
Blood from the Cubital Vein (Peripheral Blood) | |||
EDC, ×105/L | 5.12 [3.73; 5.84] | 7.25 [6.80; 7.47] Pc = 0.038 | 7.26 [5.43; 17.94] Pc = 0.037 P2 = 0.597 |
EPC, % | 4.10 [2.70; 5.00] | 6.63 [4.70; 13.00] Pc = 0.042 | 4.93 [2.20; 7.30] Pc = 0.369 P2 = 0.678 |
VEGF-A, pg/mL | 3.80 [1.00; 6.50] | 4.50 [3.00; 8.00] Pc = 0.314 | 6.00 [3.00; 9.50] Pc = 0.216 P2 = 0.502 |
VEGF-B, pg/mL | 1.32 [1.00; 3.10] | 1.60 [1.27; 2.20] Pc = 0.772 | 1.30 [1.00; 1.45] Pc = 1.000 P2 = 0.570 |
PDGF, pg/mL | 2.68 [1.65; 7.10] | 3.10 [2.10; 7.05] Pc = 1.000 | 4.85 [1.20; 9.10] Pc = 1.000 P2 = 0.870 |
SDF-1, pg/mL | 30.00 [5.00; 45.00] | 60.00 [50.00; 80.00] Pc = 0.042 | 49.00 [37.00; 56.00] Pc = 0.174 P2 = 0.115 |
MCP-1, pg/mL | 190.0 [140.0; 240.0] | 210.0 [144.4; 268.0] Pc = 0.612 | 202.5 [164.0; 324.0] Pc = 0.864 P2 = 0.527 |
Galectin-3, ng/mL | 6.50 [5.60; 7.64] | 6.10 [4.30; 7.48] Pc = 0.928 | 8.20 [7.20; 10.00] Pc = 0.025 P2 = 0.017 |
Angiopoetin-2, pg/mL | 388.0 [317.0; 460.0] | 445.0 [137.5; 552.5] Pc = 1.000 | 430.0 [380.0; 580.0] Pc = 1.000 P2 = 0.971 |
MMP-9, pg/mL | 13.20 [9.60; 19.00] | 11.95 [7.00; 13.40] Pc = 0.460 | 13.65 [6.50; 19.60] Pc = 0.848 P2 = 0.588 |
Blood from the coronary sinus (sinus blood) | |||
EDC, ×105/L | – | 10.17 [6.80; 18.83] P1 = 0.128 | 17.98 [10.27; 22.97] P1 = 0.036 P2 = 0.156 |
VEGF-A, pg/mL | – | 7.80 [3.25; 9.75] P1 = 0.041 | 6.89 [3.25; 15.60] P1 = 0.007 P2 = 0.918 |
VEGF-B, pg/mL | – | 1.00 [0.85; 1.36] P1 = 0.011 | 1.02 [0.89; 1.08] P1 = 0.285 P2 = 0.762 |
PDGF, pg/mL | – | 7.60 [3.70; 9.94] P1 = 0.036 | 7.86 [2.92; 8.77] P1 = 0.674 P2 = 0.736 |
SDF-1, pg/mL | – | 40.30 [26.00; 62.00] P1 = 0.086 | 46.80 [32.50; 64.00] P1 = 0.286 P2 = 0.623 |
MCP-1, pg/mL | – | 227.5 [135.2; 331.5] P1 = 0.209 | 242.5 [176.2; 321.8] P1 = 0.585 P2 = 0.638 |
Galectin-3, ng/mL | – | 13.13 [10.14; 15.86] P1 < 0.001 | 20.15 [14.17; 60.06] P1 < 0.001 P2 = 0.012 |
Angiopoetin-2, pg/mL | – | 767.0 [494.0; 988.0] P1 = 0.128 | 1111.5 [845.0; 1235.0] P1 < 0.001 P2 = 0.002 |
MMP-9, pg/mL | – | 5.92 [5.07; 17.42] P1 = 0.972 | 16.64 [6.63; 29.12] P1 = 0.649 P2 = 0.038 |
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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, 11, 1950. https://doi.org/10.3390/biomedicines11071950
Chumakova SP, Urazova OI, Shipulin VM, Andreev SL, Denisenko OA, Gladkovskaya MV, Litvinova LS, Bubenchikov MA. Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy. Biomedicines. 2023; 11(7):1950. https://doi.org/10.3390/biomedicines11071950
Chicago/Turabian StyleChumakova, Svetlana P., Olga I. Urazova, Vladimir M. Shipulin, Sergey L. Andreev, Olga A. Denisenko, Margarita V. Gladkovskaya, Larisa S. Litvinova, and Mikhail A. Bubenchikov. 2023. "Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy" Biomedicines 11, no. 7: 1950. https://doi.org/10.3390/biomedicines11071950
APA StyleChumakova, S. P., Urazova, O. I., Shipulin, V. M., Andreev, S. L., Denisenko, O. A., Gladkovskaya, M. V., Litvinova, L. S., & Bubenchikov, M. A. (2023). Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy. Biomedicines, 11(7), 1950. https://doi.org/10.3390/biomedicines11071950