Aim To study time-related changes in bone remodeling markers in patients with ischemic heart disease (IHD) associated with type 2 diabetes mellitus (DM) and disorders of carbohydrate metabolism (CM). Also, a possibility was studied of using these markers for evaluation of breast bone reparative regeneration in early and late postoperative periods following coronary bypass (CB).Materials and methods This study included 28 patients with IHD and functional class II-III exertional angina after CB. Patients were divided into 2 groups based on the presence (group 1) and absence (group 2) of CM disorders. Contents of osteocalcin (OC), C-terminal telopeptide (CTTP) of type 1 collagen, deoxypyridinoline (DPD), and alkaline phosphatase bone isoenzyme (ALPBI) were measured by enzyme immunoassay on admission (Т1) and at early (Т2) and late (Т3) postoperative stages. Sternal scintigraphy with a radiopharmaceutical (RP) was performed at stage 3 following sternotomy.Results The content of OC and CTTP was reduced in group 1 compared to the values in the group without CM disorders (р<0.005) at stages Т1 and Т2. There were no significant intergroup differences in concentrations of ALPBI and DPD throughout the study. Time-related changes in OC, CTTP, and DPD had some intergroup differences: the increase in biomarkers was observed in group 1 considerably later, at stage Т3 (р<0.005), while in group 2, it was observed at stage T2 after sternotomy. Scintigraphy revealed significant intergroup differences in the intensity of RP accumulation in sternal tissue.Conclusion The intergroup differences in the content of biomarkers evidenced a disbalance among processes of formation and resorption of bone tissue and delayed remodeling processes in patients with IHD associated with type 2 DM and CM disorders. The study confirmed significance of comprehensive evaluation of time-related changes in markers for bone tissue metabolism and sternal scintigraphy for diagnosis and evaluation of sternal reparative regeneration following sternotomy in patients with IHD associated with type 2 DM and disorders of CM metabolism.
Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Ministry of Science and Higher Education of Russian Federation T regulatory lymphocytes (Treg) participate in resolution of inflammation and are essential in post-infarct myocardial healing. The crucial mediator of Treg activity is transcription factor FoxP3. Nuclear localization of FoxP3 is an obligatory requirement for anti-inflammatory properties of the cells. FoxP3 is also expressed in conventional T-lymphocytes at the stage of their activation. Data on functional state of FoxP3 in chronic and acute coronary syndromes are absent. Purpose Our aim was to comparatively evaluate the level of FoxP3 nuclear translocation in subpopulations of FoxP3+ T-lymphocytes in patients with chronic and acute coronary syndromes. Methods We have recruited 14 patients with chronic coronary syndrome (CCS) (8 males; 6 females; 63.2 ± 9.0 y.o.) and 5 patients with acute anterior ST-segment elevation myocardial infarction (STEMI) (4 males; 1 female; 61.4 ± 11.2 y.o.). Reperfusion of the infarct-related artery (IRA) has been achieved in all STEMI patients (the mean time of recanalization constituted 5 hours), and coronary angioplasty and IRA stenting were performed. Health status was evaluated and functional class of chronic heart failure was assessed according to the 6-minute walk test. Peripheral blood mononuclear cells were isolated from heparinized blood of CCS patients and STEMI patients during the first day after the event. Frequency of T regulatory and T conventional lymphocytes and degree of FoxP3 nuclear translocation in them were evaluated by imaging flow cytometry. Results Numbers of T regulatory lymphocytes in STEMI patients were lower than in patients with CCS, while numbers of T conventional lymphocytes were higher. However these differences did not reach the level of statistical significance: 7.2 (6.2; 8.4)% vs. 6.7 (3.8; 7.0)% of T regulatory lymphocytes (p = 0.298) and 1.6 (1.3; 1.8)% vs. 2.1 (1.0; 2.8)% of T conventional cells (p = 0.754), in CCS and in STEMI patients, respectively. Meanwhile, STEMI patients displayed significantly lower nuclear translocation of FoxP3 in lymphocytes compared to CCS patients: 74.8 (64.9; 92.9)% vs. 98.2 (96.8; 98.7)% in T regulatory cells (p = 0.026) and 58.7 (33.9; 67.7)% vs. 88.3 (73.1; 96.9)% in T conventional lymphocytes (p = 0.034). Conclusions Our study is the first one to comparatively describe the FoxP3 nuclear translocation in patients with chronic coronary syndrome and STEMI. We showed that STEMI is primarily associated with the decrease of nuclear localization of FoxP3 rather than with changes in numbers of FoxP3+ T-lymphocytes in peripheral blood. The revealed phenomenon demonstrates that alterations of the balance between the suppressive and inflammatory activities of T-lymphocytes are observed already in the early inflammatory phase of STEMI, long before their expected clonal expansion.
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