Pathogenetic role of apoptosis biomarker expression in patients with chronic obstructive pulmonary disease and concomitant arterial hypertension: a literature review
DOI:
https://doi.org/10.14739/2409-2932.2026.1.350736Keywords:
arterial hypertension, chronic obstructive pulmonary disease, apoptosis, caspases, cytokinesAbstract
It is well known that chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH) are multifactorial diseases that develop as a result of complex interactions between genetic and environmental factors. Both internal and external factors can cause the activation of apoptosis, which is considered to be the key factor in the accelerated degradation and death of cells, leading to structural and functional disorders in organs. Apoptosis processes are initiated in the cells of affected organs long before the clinical manifestations of the disease become noticeable. Research and study of the triggering factors and pathobiology of apoptosis in AH and COPD can help to optimise screening programmes for the detection of these diseases in the early preclinical stages and develop new effective targeted treatment regimens based on blocking individual apoptosis pathways in cells.
The aim of the study is to investigate the characteristics of the synthesis, metabolism and regulation of molecules, receptors and ligands involved in apoptosis in patients with COPD and AH.
Materials and methods. For a systematic review of the literature, reviewed scientific articles indexed in leading scientometric databases (PubMed, Scopus, Google Scholar, and Web of Science) were used.
Results. Apoptosis is a complex and multi-component process of programmed cell death. It has been proven that the processes of apoptosis in vascular endothelial cells, bronchial epithelial cells, and smooth muscle cells of the vascular and bronchial walls are significantly accelerated and scaled up in conditions of comorbid COPD and AH. Various molecules, ligands, and receptors are involved in the cascade of apoptotic changes, namely caspases 3, 7, 8, and 9, active forms of oxygen, calcium-dependent proteases, cytochrome C, parkin-4, Bcl-2 family proteins, apoptosis-related protein activator factor 1 (APAF-1), heat shock proteins, tumour necrosis factor, Fas ligand, Bax and p53 proteins, and soluble messenger proteins such as MFG-E8.
Conclusions. There is a correlation between the dynamics of markers of apoptotic processes on the one hand and the severity of respiratory and haemodynamic disorders in COPD comorbidity with AH on the other. A detailed study of the mechanisms of initiation and regulation of neutrophil apoptosis involving cysteine proteases and other markers of apoptosis in patients with comorbid COPD and AH is a promising area of current research. Such data may form the basis for the correction of therapeutic regimens and allow for the optimisation of treatment.
References
Mustafa M, Ahmad R, Tantry IQ, Ahmad W, Siddiqui S, Alam M, et al. Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications. Cells. 2024;13(22):1838. doi: https://doi.org/10.3390/cells13221838
Chaves SR, Rego A, Santos-Pereira C, Sousa MJ, Côrte-Real M. Current and novel approaches in yeast cell death research. Cell Death Differ. 2025;32(2):207-18. doi: https://doi.org/10.1038/s41418-024-01298-2
Mahajan A, Sharma G, Thakur K, Raza K, Singh G, Katare OP. Autoimmune diseases and apoptosis: Targets, challenges, and innovations. In: Clinical Perspectives and Targeted Therapies in Apoptosis. Elsevier; 2021. p. 285-327. Available from: https://doi.org/10.1016/B978-0-12-815762-6.00009-3
Boutouyrie P, Chowienczyk P, Humphrey JD, Mitchell GF. Arterial Stiffness and Cardiovascular Risk in Hypertension. Circ Res. 2021;128(7):864-86. doi: https://doi.org/10.1161/CIRCRESAHA.121.318061
Almanzar G, Alarcon JC, Garzon R, Navarro AM, Ondo-Méndez A, Prelog M. Hypoxia and activation of hypoxia inducible factor alpha as influencers of inflammatory helper T cells in autoimmune disease - a link between cancer and autoimmunity. Front Immunol. 2025;16:1633845. doi: https://doi.org/10.3389/fimmu.2025.1633845
Lalier L, Vallette F, Manon S. Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death. Biomolecules. 2022;12(2):162. doi: https://doi.org/10.3390/biom12020162
Nguyen T, Gillet G, Popgeorgiev N. Caspases in the Developing Central Nervous System: Apoptosis and Beyond. Front Cell Dev Biol. 2021;9:702404. doi: https://doi.org/10.3389/fcell.2021.702404
Green DR. The Death Receptor Pathway of Apoptosis. Cold Spring Harb Perspect Biol. 2022;14(2):a041053. doi: https://doi.org/10.1101/cshperspect.a041053
Voss AK, Strasser A. The essentials of developmental apoptosis. F1000Res. 2020;9:F1000 Faculty Rev-148. doi: https://doi.org/10.12688/f1000research.21571.1
Macrì F, Vigorito I, Castiglione S, Faggiano S, Casaburo M, Fanotti N, et al. High Phosphate-Induced JAK-STAT Signalling Sustains Vascular Smooth Muscle Cell Inflammation and Limits Calcification. Biomolecules. 2023;14(1):29. doi: https://doi.org/10.3390/biom14010029
Cao Y, Cao Y, Liu J, Ye Y, Jiang M. Comprehensive Review of Mechanisms and Translational Perspectives on Programmed Cell Death in Vascular Calcification. Biomolecules. 2025;15(12):1640. doi: https://doi.org/10.3390/biom15121640
Gagliardi M, Ashizawa AT. Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2. Pharmaceutics. 2022;14(1):97. doi: https://doi.org/10.3390/pharmaceutics14010097
Guedes JP, Mendes F, Machado BO, Manon S, Côrte-Real M, Chaves SR. Yeast NatB Regulates Cell Death of Bax-Expressing Cells. Biomolecules. 2025 Dec 12;15(12):1731. doi: https://doi.org/10.3390/biom15121731
Gupta VA, Ackley J, Kaufman JL, Boise LH. BCL2 Family Inhibitors in the Biology and Treatment of Multiple Myeloma. Blood Lymphat Cancer. 2021;11:11-24. doi: https://doi.org/10.2147/BLCTT.S245191
Li M. The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases. Apoptosis. 2021;26(5-6):235-47. doi: https://doi.org/10.1007/s10495-021-01667-z
Dabravolski SA, Markin AM, Andreeva ER, Eremin II, Orekhov AN, Melnichenko AA. Emerging role of pericytes in therapy of cardiovascular diseases. Biomed Pharmacother. 2022;156:113928. doi: https://doi.org/10.1016/j.biopha.2022.113928
Guedes JP, Boyer JB, Elurbide J, Carte B, Redeker V, Sago L, et al. NatB Protects Procaspase-8 from UBR4-Mediated Degradation and Is Required for Full Induction of the Extrinsic Apoptosis Pathway. Mol Cell Biol. 2024;44(9):358-71. doi: https://doi.org/10.1080/10985549.2024.2382453
Zykova SS, Gessel T, Galembikova A, Mozhaitsev ES, Borisevich SS, Igidov N, et al. Hypoxia-Inducible Factor-1α, a Novel Molecular Target for a 2-Aminopyrrole Derivative: Biological and Molecular Modeling Study. Cancers (Basel). 2025;18(1):115. doi: https://doi.org/10.3390/cancers18010115
Yang L, Dai R, Wu H, Cai Z, Xie N, Zhang X, et al. Unspliced XBP1 Counteracts β-Catenin to Inhibit Vascular Calcification. Circ Res. 2022;130(2):213-29. doi: https://doi.org/10.1161/CIRCRESAHA.121.319745
Guedes JP, Baptista V, Santos-Pereira C, Sousa MJ, Manon S, Chaves SR, et al. Acetic acid triggers cytochrome c release in yeast heterologously expressing human Bax. Apoptosis. 2022;27(5-6):368-81. doi: https://doi.org/10.1007/s10495-022-01717-0
Feoktistova M, Makarov R, Yazdi AS, Panayotova-Dimitrova D. RIPK1 and TRADD Regulate TNF-Induced Signaling and Ripoptosome Formation. Int J Mol Sci. 2021;22(22):12459. doi: https://doi.org/10.3390/ijms222212459
Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, et al. Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer. Signal Transduct Target Ther. 2023;8(1):204. doi: https://doi.org/10.1038/s41392-023-01468-7
Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 2022;29(5):946-60. doi: https://doi.org/10.1038/s41418-022-00988-z
Rego A, Ribeiro A, Côrte-Real M, Chaves SR. Monitoring yeast regulated cell death: trespassing the point of no return to loss of plasma membrane integrity. Apoptosis. 2022;27(9-10):778-86. doi: https://doi.org/10.1007/s10495-022-01748-7
Zhang C, Liu J, Wang J, Zhang T, Xu D, Hu W, et al. The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer. Front Cell Dev Biol. 2021;9:648808. doi: https://doi.org/10.3389/fcell.2021.648808
Vidavsky N, Kunitake J, Estroff LA. Multiple Pathways for Pathological Calcification in the Human Body. Adv Healthc Mater. 2021;10(4):e2001271. doi: https://doi.org/10.1002/adhm.202001271
Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol. 2022;12:985363. doi: https://doi.org/10.3389/fonc.2022.985363
Liang J, Zhao W, Tong P, Li P, Zhao Y, Li H, et al. Comprehensive molecular characterization of inhibitors of apoptosis proteins (IAPs) for therapeutic targeting in cancer. BMC Med Genomics. 2020;13(1):7. doi: https://doi.org/10.1186/s12920-020-0661-x
Shi X, Yan K, Ding R, Ma Y, Liang Q, Sun Z. Long-term exposure to silica nanoparticles induces DNA damage by activating ferritinophagy in the lungs. Ecotoxicol Environ Saf. 2026;310:119723. doi: https://doi.org/10.1016/j.ecoenv.2026.119723
Liu N, Meng B, Zeng L, Yin S, Hu Y, Li S, et al. Discovery of a novel rice-derived peptide with significant anti-gout potency. Food Funct. 2020;11(12):10542-53. doi: https://doi.org/10.1039/d0fo01774d
Cui Y, Luo L, Zeng Z, Liu X, Li T, He X, et al. MFG-E8 stabilized by deubiquitinase USP14 suppresses cigarette smoke-induced ferroptosis in bronchial epithelial cells. Cell Death Dis. 2023;14(1):2. doi: https://doi.org/10.1038/s41419-022-05455-8
Heinbockel L, Marwitz S, Schromm AB, Watz H, Kugler C, Ammerpohl O, et al. Identification of novel target genes in human lung tissue involved in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2018;13:2255-9. doi: https://doi.org/10.2147/COPD.S161958
Wang D, Liu W, Wang L, Zhang N, Huang X, Chen H. Association of the single-nucleotide polymorphism in the MFG-E8 gene with coronary heart disease in Chinese Han population. BMC Cardiovasc Disord. 2025;25(1):397. doi: https://doi.org/10.1186/s12872-025-04860-z
Ruotsalainen SE, Surakka I, Mars N, Karjalainen J, Kurki M, Kanai M, et al. Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis. Commun Biol. 2022;5(1):802. doi: https://doi.org/10.1038/s42003-022-03552-0
Aliyar AA, Eldar AS, Sadig SA, Mubariz GT, Adil MN, Aydın AS. Advances in the Study of Bronchial and Vascular Architecture of Lungs in the Rat's Model: from Morphogenesis to Disease Modelling. Cell Physiol Biochem. 2025;59(6). doi: https://doi.org/10.33594/000000834
Jiang A, Li J, He Z, Liu Y, Qiao K, Fang Y, et al. Renal cancer: signaling pathways and advances in targeted therapies. MedComm (2020). 2024;5(8):e676. doi: https://doi.org/10.1002/mco2.676
Citi V, Fallica AN, Salerno L, Virzì NF, Ciaffaglione V, Intagliata S, et al. Semi-Synthetic H2S Releasing Compounds with Antioxidant and Vasorelaxant Properties. ACS Med Chem Lett. 2025;17(1):199-210. doi: https://doi.org/10.1021/acsmedchemlett.5c00624
Unnisa A, Greig NH, Kamal MA. Inhibition of Caspase 3 and Caspase 9 Mediated Apoptosis: A Multimodal Therapeutic Target in Traumatic Brain Injury. Curr Neuropharmacol. 2023;21(4):1001-1012. doi: https://doi.org/10.2174/1570159X20666220327222921
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 O. V. Kraidashenko, R. L. Kulynych, O. S. Tiahla, O. O. Soloviuk, V. V. Yakymenko, M. O. Panasenko
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
