Identification and Validation of Novel Biomarkers Related to the Calcium Metabolism Pathway in Hypertension Patients Based on Comprehensive Bioinformatics Methods — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Identification and Validation of Novel Biomarkers Related to the Calcium Metabolism Pathway in Hypertension Patients Based on Comprehensive Bioinformatics Methods
Department of Laboratory, Yangbi Yi Autonomous County People’s Hospital, Dali, China
,
Department of Obstetrics and Gynecology, Yangbi Yi Autonomous County People’s Hospital, Dali, China
,
Department of Laboratory, Yangbi Yi Autonomous County People’s Hospital, Dali, China
,
Department of Infectious Diseases, Yangbi Yi Autonomous County People’s Hospital, Dali, China
,
Medical Community Office, Yangbi Yi Autonomous County People’s Hospital, Dali, China
1 Department of Laboratory, Yangbi Yi Autonomous County People’s Hospital, Dali, China
2 Department of Obstetrics and Gynecology, Yangbi Yi Autonomous County People’s Hospital, Dali, China
3 Department of Laboratory, Yangbi Yi Autonomous County People’s Hospital, Dali, China
4 Department of Infectious Diseases, Yangbi Yi Autonomous County People’s Hospital, Dali, China
5 Medical Community Office, Yangbi Yi Autonomous County People’s Hospital, Dali, China
Background: Hypertension is a universal risk factor for cardiovascular diseases and is thus the leading cause of death worldwide. The identification of novel prognostic and pathogenesis biomarkers plays a key role in diseas e management. Methods: The GSE145854 and GSE164494 datasets were downloa ded from the Gene Expression Omnibus (GEO) database and used f or s creening and validating hypertension signature genes, respectively. Gen e Ontology (GO) enrichment analysis was performed on the differentially expressed genes (DEGs) related to calcium ion metabolism in patients with hypertension. The core genes related to immune infiltration were analyzed and screened, and the activity of the signature genes and related pathways was quantified using gene set enrichment analysis (GSEA). The infiltration of immune cells in the blood samples was analyzed, and the DEGs that were abnormally expressed in the clinical blood samples of patients with hypertension were verified via RT - qPCR. Results: A total of 176 DEGs were screened. GO showed that DEGs was involved in the regulation of calcium ion met abol ism in biological processes (BP), actin mediated cell contraction, negative regulation of cell movement, and calcium ion transmembrane transport, and i n the regulation of protease activity in molecular functions (MF). KEGG analy sis revealed that the DEGs were involved mainly in the cGMP - PKG signalin g pathway, ubiquitin-protein transferase, tight junction-associated pro teins, and the regulation of myocardial cells. MF analysis revealed the immune infiltration function of the cells. RT - qPCR revealed that the expression of Cacna1d, Serpine1, Slc8a3, and Trpc4 was up regulated in hypertension, the expression of Myoz2 and Slc25a23 was down regulated. Conclusion: Cacna1d, Serpine1, Slc8a3, Trpc4, Myoz2 and Slc25a23 may be involved in the regulation of calcium metabolism pathways and play key roles in hypertension. These differentially expressed calcium metabolism-related genes may serve as prognostic markers of hypertension.
Smereczańska, M., Domian, N., Młynarczyk, M., et al. (2023) Evaluation of the Expression and Localization of the Multifunctional Protein CacyBP/SIP and Elements of the MAPK Signaling Pathway in the Adrenal Glands of Rats with Primary and Secondary Hypertension. International Journal of Molecular Sciences, 25, Article No. 84. https://doi.org/10.3390/ijms25010084
Gharipour, M., Nezafati, P., Sadeghian, L., et al. (2022) Precision Medicine and Metabolic Syndrome. ARYA Atherosclerosis, 18, 1-10.
Buford, T. (2016) Hypertension and Aging. Aging Research Reviews, 26, 96-111. https://doi.org/10.1016/j.arr.2016.01.007
Zhou, D., Xi, B., Zhao, M., et al. (2018) Uncontrolled Hypertension Increases Risk of All-Cause and Cardiovascular Disease Mortality in US Adults: The NHANES III Linked Mortality Study. Scientific Reports, 8, Article No. 9418. https://doi.org/10.1038/s41598-018-27377-2
Deussen, A. and Kopaliani, I. (2023) Targeting Inflammation in Hypertension. Current Opinion in Nephrology and Hypertension, 32, 111-117. https://doi.org/10.1097/MNH.0000000000000862
Zhu, Y., Yang, X. and Zu, Y. (2022) Integrated Analysis of WGCNA and Machine Learning Identified Diagnostic Biomarkers in Dilated Cardiomyopathy with Heart Failure. Frontiers in Cell and Developmental Biology, 10, Article ID: 1089915. https://doi.org/10.3389/fcell.2022.1089915
Orlov, Y., Anashkina, A., Klimontov, V., et al. (2021) Medical Genetics, Genomics and Bioinformatics Aid in Understanding Molecular Mechanisms of Human Diseases. International Journal of Molecular Sciences, 22, Article No. 9962. https://doi.org/10.3390/ijms22189962
Picard, M., Scott-Boyer, M., Bodein, A., et al. (2021) Integration Strategies of Multiomics Data for Machine Learning Analysis. Computational and Structural Biotechnology Journal, 19, 3735-3746. https://doi.org/10.1016/j.csbj.2021.06.030
Zheng, T., Zheng, Z., Zhou, H., et al. (2023) The Multifaceted Roles of COL4A4 in Lung Adenocarcinoma: An Integrated Bioinformatics and Experimental Study. Computers in Biology and Medicine, 170, Article ID: 107896. https://doi.org/10.1016/j.compbiomed.2023.107896
Zhou, X., Chen, Y., Zhang, Z., et al. (2024) Identification of Differentially Expressed Genes, Signaling Pathways and Immune Infiltration in Postmenopausal Osteoporosis by Integrated Bioinformatics Analysis. Heliyon, 10, E23794. https://doi.org/10.1016/j.heliyon.2023.e23794
Klinik Für Innere Medizin III A E N, Universitätsklinikum Jena, Jena, Germany (2019) Recent Advances in Hypertension Research. Acta Physiologica (Oxford, England), 226, E13295.
Bioinformatics Analysis
Wei, Y., George, N., Chang, C., et al. (2017) Assessing Sex Differences in the Risk of Cardiovascular Disease and Mortality per Increment in Systolic Blood Pressure: A Systematic Review and Meta-Analysis of Follow-Up Studies in the United States. PLOS ONE, 12, E0170218. https://doi.org/10.1371/journal.pone.0170218
Eid, A., El-Yazbi, A., Zouein, F., et al. (2018) Inositol 1,4,5-Trisphosphate Receptors in Hypertension. Frontiers in Physiology, 9, Article No. 1018. https://doi.org/10.3389/fphys.2018.01018
Ma, J., Li, Y., Yang, X., et al. (2023) Signaling Pathways in Vascular Function and Hypertension: Molecular Mechanisms and Therapeutic Interventions. Signal Transduction and Targeted Therapy, 8, Article No. 168. https://doi.org/10.1038/s41392-023-01430-7
Pan, X., Shao, Y., Wu, F., et al. (2018) FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice. Cell Metabolism, 27, 1323-1337.E5. https://doi.org/10.1016/j.cmet.2018.04.002
Wilson, C., Zhang, X., Buckley, C., et al. (2019) Increased Vascular Contractility in Hypertension Results from Impaired Endothelial Calcium Signaling. Hypertension (Dallas, Tex: 1979), 74, 1200-1214. https://doi.org/10.1161/HYPERTENSIONAHA.119.13791
Zhang, Z., Zhao, L., Zhou, X., et al. (2022) Role of Inflammation, Immunity, and Oxidative Stress in Hypertension: New Insights and Potential Therapeutic Targets. Frontiers in Immunology, 13, Article ID: 1098725. https://doi.org/10.3389/fimmu.2022.1098725
Pioli, M. and De Faria, A. (2019) Pro-Inflammatory Cytokines and Resistant Hypertension: Potential for Novel Treatments? Current Hypertension Reports, 21, Article No. 95. https://doi.org/10.1007/s11906-019-1003-2
Teixeira, D., Peruchetti, D., Souza, M., et al. (2020) A High Salt Diet Induces Tubular Damage Associated with a Pro-Inflammatory and Pro-Fibrotic Response in a Hypertension-Independent Manner. Biochimica et Biophysica Acta Molecular Basis of Disease, 1866, Article ID: 165907. https://doi.org/10.1016/j.bbadis.2020.165907
Giorgi, C., Danese, A., Missiroli, S., et al. (2018) Calcium Dynamics as a Machine for Decoding Signals. Trends in Cell Biology, 28, 258-273. https://doi.org/10.1016/j.tcb.2018.01.002
Marchi, S., Giorgi, C., Galluzzi, L., et al. (2020) Ca Fluxes and Cancer. Molecular Cell, 78, 1055-1069. https://doi.org/10.1016/j.molcel.2020.04.017
Lei, M., Wu, L., Terrar, D., et al. (2018) Modernized Classification of Cardiac Antiarrhythmic Drugs. Circulation, 138, 1879-1896. https://doi.org/10.1161/CIRCULATIONAHA.118.035455
Tiscione, S., Casas, M., Horvath, J., et al. (2021) IP3R-Driven Increases in Mitochondrial Ca2+ Promote Neuronal Death in NPC Disease. Proceedings of the National Academy of Sciences of the United States of America, 118, e2110629118. https://doi.org/10.1073/pnas.2110629118
Cui, C., Merritt, R., Fu, L., et al. (2017) Targeting Calcium Signaling in Cancer Therapy. Acta Pharmaceutica Sinica B, 7, 3-17. https://doi.org/10.1016/j.apsb.2016.11.001
Stearman, R., Bui, Q., Speyer, G., et al. (2019) Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome. American Journal of Respiratory Cell and Molecular Biology, 60, 637-649. https://doi.org/10.1165/rcmb.2018-0368OC
Saygin, D., Tabib, T., Bittar, H., et al. (2020) Transcriptional Profiling of Lung Cell Populations in Idiopathic Pulmonary Arterial Hypertension. Pulmonary Circulation, 10, 1-15. https://doi.org/10.1177/2045894020908782
Rahman, M., Rana, H., Peng, S., et al. (2021) Bioinformatics and Machine Learning Methodologies to Identify the Effects of Central Nervous System Disorders on Glioblastoma Progression. Briefings in Bioinformatics, 22, bbaa365. https://doi.org/10.1093/bib/bbaa365
Rahman, M., Peng, S., Hu, X., et al. (2020) A Network-Based Bioinformatics Approach to Identify Molecular Biomarkers for Type 2 Diabetes That Are Linked to the Progression of Neurological Diseases. International Journal of Environmental Research and Public Health, 17, Article No. 1035. https://doi.org/10.3390/ijerph17031035
Lu, X., Wang, L., Lin, X., et al. (2015) Genome-Wide Association Study in Chinese Identifies Novel Loci for Blood Pressure and Hypertension. Human Molecular Genetics, 24, 865-874. https://doi.org/10.1093/hmg/ddu478
Stanton, A., Heydarpour, M., Williams, J., et al. (2023) CACNA1D Gene Polymorphisms Associate with Increased Blood Pressure and Salt Sensitivity of Blood Pressure in White Individuals. Hypertension (Dallas, Tex: 1979), 80, 2665-2673. https://doi.org/10.1161/HYPERTENSIONAHA.123.21229
Pande, J., Mallhi, K., Sawh, A., et al. (2006) Aortic Smooth Muscle and Endothelial Plasma Membrane Ca2+ Pump Isoforms Are Inhibited Differently by the Extracellular Inhibitor Caloxin 1b1. American Journal of Physiology Cell Physiology, 290, C1341-C1349. https://doi.org/10.1152/ajpcell.00573.2005