Role of angiotensin II and neuroendocrine factors in immunological regulation in patients with coronary heart disease: prospective cross-sectional study

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Abstract

BACKGROUND: Among chronic noncommunicable diseases, cardiovascular diseases, particularly coronary heart disease (CHD), are the leading cause of death. The rennin-angiotensin-aldosterone system plays an important role in CHD development and progression; however, its role in the regulation of immunoneuroendocrine interactions requires further analysis.

OBJECTIVE: To study the relationship between angiotensin II (AT II) and molecular regulators of the activity of whole blood mononuclear cells (MNCs) in patients with angina pectoris.

MATERIALS AND METHODS: This cross-sectional study enrolled 65 patients with exertional angina aged 45–67 years, including 19 apparently healthy individuals. The levels of interleukins (ILs), transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PG E2), serotonin, thyroid-stimulating hormone (TSH), and AT II in the blood serum were determined. In MNCs, the concentrations of protein kinases FAK, JNK, p38, and ERK, signal transducers, and activators of transcription (STAT 3, 5A, and 6) were determined.

RESULTS: In patients with coronary artery disease, the production of TGF-β1 increased by 7.2% (p=0.00001), AT II by 136.9% (p=0.0001), serotonin by 129.0% (p=0.00001), IL-18 by 92.5% (p=0.00001), TSH by 51.7% (p=0.0012), ERK protein kinase content by 86.4% (p=0.0001), JNK by 56.8% (p=0.0001), and FAK by 55.3% (p=0.00002). The levels of IL-15 also decreased by 38.1% (p=0.0001), PG E2 by 39.5% (p=0.0001), and STAT3 by 52.5% (p=0.0001).

CONCLUSION: The nature of the identified relationships among the analyzed factors allows us to consider AT II as a factor that ensures adaptive coupling of immune and neuroendocrine regulatory mechanisms in patients with coronary artery disease, contributing to a change in the balance between macrophages and T-helper types 1 and 2.

About the authors

Vladimir K. Parfenyuk

Razumovsky Saratov State Medical University

Email: parfenyk0111@mail.ru
ORCID iD: 0000-0003-1329-4178
SPIN-code: 8154-2179

МD, Dr Sci. (Med.),  department professor

Russian Federation, Saratov

Anna V. Logatkina

Tula State University

Email: Logatkina_a@mail.ru
ORCID iD: 0000-0002-3397-136X
SPIN-code: 5365-6058

graduate student

Russian Federation, Tula

Stanislav S. Bondar

Kaluga Regional Clinical Hospital

Email: stos34@list.ru
ORCID iD: 0000-0003-2749-8366
SPIN-code: 6644-6951

therapist

Russian Federation, Kaluga

Igor V. Terekhov

Tsiolkovsky Kaluga State University

Author for correspondence.
Email: trft@mail.ru
ORCID iD: 0000-0002-6548-083X
SPIN-code: 2798-1551

МD, Cand Sci. (Med.), associate professor

Russian Federation, Kaluga

Viktor S. Nikiforov

Mechnikov North-Western State Medical University

Email: viktor.nikiforov@szgmu.ru
ORCID iD: 0000-0001-7862-0937
SPIN-code: 4652-0981

МD, Dr Sci. (Med.), department professor

Russian Federation, St. Petersburg

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2. Fig. 1. Relationships between the studied factors in patients with coronary artery disease (original drawing).

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3. direction of regulation

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4. influence of the factor on the functional activity of the corresponding MNC populations

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5. nfluence of the factor on the regulation of gene expression and/or intracellular processes

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