{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:13Z","timestamp":1786977013833,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP13s-0213-200352"],"award-info":[{"award-number":["NPRP13s-0213-200352"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["UREP27-050-3-020"],"award-info":[{"award-number":["UREP27-050-3-020"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertension is a pervasive and widespread health condition that poses a significant risk factor for cardiovascular disease, which includes conditions such as heart attack, stroke, and heart failure. Despite its widespread occurrence, the exact cause of hypertension remains unknown, and the mechanisms underlying the progression from prehypertension to hypertension require further investigation. Recent proteomic studies have shown promising results in uncovering potential biomarkers related to disease development. In this study, serum proteomic data collected from Qatar Biobank were analyzed to identify altered protein expression between individuals with normal blood pressure, prehypertension, and hypertension and to elucidate the biological pathways contributing to this disease. The results revealed a cluster of proteins, including the SRC family, CAMK2B, CAMK2D, TEC, GSK3, VAV, and RAC, which were markedly upregulated in patients with hypertension compared to those with prehypertension (fold change \u2265 1.6 or \u2264\u22121.6, area under the curve \u2265 0.8, and q-value &lt; 0.05). Pathway analysis showed that the majority of these proteins play a role in actin cytoskeleton remodeling. Actin cytoskeleton reorganization affects various biological processes that contribute to the maintenance of blood pressure, including vascular tone, endothelial function, cellular signaling, inflammation, fibrosis, and mechanosensing. Therefore, the findings of this study suggest a potential novel role of actin cytoskeleton-related proteins in the progression from prehypertension to hypertension. The present study sheds light on the underlying pathological mechanisms involved in hypertension and could pave the way for new diagnostic and therapeutic approaches for the treatment of this disease.<\/jats:p>","DOI":"10.3390\/ijms25094896","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T03:30:49Z","timestamp":1714534249000},"page":"4896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-392X","authenticated-orcid":false,"given":"Sarah","family":"Al Ashmar","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulsen Guliz","family":"Anlar","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-0060","authenticated-orcid":false,"given":"Hubert","family":"Krzyslak","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aalborg University Hospital, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiche","family":"Djouhri","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-237X","authenticated-orcid":false,"given":"Layla","family":"Kamareddine","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar"},{"name":"Biomedical Research Center, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-0293","authenticated-orcid":false,"given":"Shona","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-6555","authenticated-orcid":false,"given":"Asad","family":"Zeidan","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.7326\/M17-3203","article-title":"Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Synopsis of the 2017 American College of Cardiology\/American Heart Association Hypertension Guideline","volume":"168","author":"Carey","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_2","unstructured":"WHO (2024, January 21). Hypertension. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hypertension."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"235101","DOI":"10.1155\/2015\/235101","article-title":"Prevalence of Cardiovascular Disease and Associated Risk Factors among Adult Population in the Gulf Region: A Systematic Review","volume":"2015","author":"Aljefree","year":"2015","journal-title":"Adv. Public Health"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Al-Thani, M.H., Al-Mutawa, K.A., Alyafei, S.A., Ijaz, M.A., Khalifa, S.A.H., Kokku, S.B., Mishra, A.C.M., Poovelil, B.V., Soussi, M.B., and Toumi, A.A. (2021). Characterizing epidemiology of prediabetes, diabetes, and hypertension in Qataris: A cross-sectional study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0259152"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","article-title":"2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)","volume":"41","author":"Mancia","year":"2023","journal-title":"J. Hypertens."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.je.2016.08.001","article-title":"Progression from prehypertension to hypertension and risk of cardiovascular disease","volume":"27","author":"Ishikawa","year":"2017","journal-title":"J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12933-021-01356-w","article-title":"Autonomic nervous system activity changes in patients with hypertension and overweight: Role and therapeutic implications","volume":"20","author":"Valensi","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40885-018-0102-8","article-title":"Arterial stiffness and hypertension","volume":"24","author":"Oh","year":"2018","journal-title":"Clin. Hypertens."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1161\/HYPERTENSIONAHA.120.15026","article-title":"2020 International Society of Hypertension Global Hypertension Practice Guidelines","volume":"75","author":"Unger","year":"2020","journal-title":"Hypertension"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1161\/01.HYP.0000167152.98618.4b","article-title":"Management of Prehypertension","volume":"45","author":"Svetkey","year":"2005","journal-title":"Hypertension"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1161\/01.CIR.101.3.329","article-title":"Essential Hypertension","volume":"101","author":"Oparil","year":"2000","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/jhh.2012.30","article-title":"Proteomics in hypertension","volume":"27","author":"Carty","year":"2013","journal-title":"J. Hum. Hypertens."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/14789450.2019.1632197","article-title":"Proteomic investigations into hypertension: What\u2019s new and how might it affect clinical practice?","volume":"16","author":"Padial","year":"2019","journal-title":"Expert. Rev. Proteom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/ajh\/hpy083","article-title":"Hypertension Induced Morphological and Physiological Changes in Cells of the Arterial Wall","volume":"31","author":"McCarthy","year":"2018","journal-title":"Am. J. Hypertens."},{"key":"ref_15","first-page":"23","article-title":"Mitogen-activated protein kinases as biomarkers of hypertension or cardiac pressure overload","volume":"55","author":"Ocaranza","year":"2010","journal-title":"Am. Heart Assoc."},{"key":"ref_16","first-page":"273","article-title":"Phosphatidylinositol 3-kinase: A key regulator of vascular tone?","volume":"91","author":"Sata","year":"2002","journal-title":"Am. Heart Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ramos-Kuri, M., Meka, S.H., Salamanca-Buentello, F., Hajjar, R.J., Lipskaia, L., and Chemaly, E.R. (2021). Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies. Biol. Res., 54.","DOI":"10.1186\/s40659-021-00342-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bbacli.2014.10.001","article-title":"Quantitative proteomics reveals novel therapeutic and diagnostic markers in hypertension","volume":"2","author":"Matafora","year":"2014","journal-title":"BBA Clin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1161\/HYPERTENSIONAHA.116.08906","article-title":"Proteomic-Biostatistic Integrated Approach for Finding the Underlying Molecular Determinants of Hypertension in Human Plasma","volume":"70","author":"Gajjala","year":"2017","journal-title":"Hypertension"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12964-021-00750-x","article-title":"Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition","volume":"19","author":"Ortiz","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.7150\/ijms.49241","article-title":"Src-family Protein Tyrosine Kinases: A promising target for treating Cardiovascular Diseases","volume":"18","author":"Zhai","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7957","DOI":"10.1038\/sj.onc.1208079","article-title":"The interplay between Src family kinases and receptor tyrosine kinases","volume":"23","author":"Bromann","year":"2004","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7928","DOI":"10.1038\/sj.onc.1208080","article-title":"The interplay between Src and integrins in normal and tumor biology","volume":"23","author":"Playford","year":"2004","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.bbamcr.2009.06.002","article-title":"Formin-binding proteins: Modulators of formin-dependent actin polymerization","volume":"1803","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Qin, B., and Zhou, J. (2015). Src Family Kinases (SFK) Mediate Angiotensin II-Induced Myosin Light Chain Phosphorylation and Hypertension. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127891"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1091\/mbc.e06-03-0252","article-title":"CaMKII\u03b2 Association with the Actin Cytoskeleton Is Regulated by Alternative Splicing","volume":"17","author":"Lasda","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bhattacharyya, M., Karandur, D., and Kuriyan, J. (2020). Structural Insights into the Regulation of Ca(2+)\/Calmodulin-Dependent Protein Kinase II (CaMKII). Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a035147"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00395-018-0688-8","article-title":"Physiological and unappreciated roles of CaMKII in the heart","volume":"113","author":"Beckendorf","year":"2018","journal-title":"Basic. Res. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.yjmcc.2018.10.010","article-title":"Cardiac CaMKII activation promotes rapid translocation to its extra-dyadic targets","volume":"125","author":"Wood","year":"2018","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.yjmcc.2019.01.001","article-title":"CaMKII signaling in heart diseases: Emerging role in diabetic cardiomyopathy","volume":"127","author":"Hegyi","year":"2019","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15239","DOI":"10.1074\/jbc.275.20.15239","article-title":"Ca2+\/calmodulin-dependent kinase II and calcineurin play critical roles in endothelin-1-induced cardiomyocyte hypertrophy","volume":"275","author":"Zhu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cipolletta, E., Rusciano, M.R., Maione, A.S., Santulli, G., Sorriento, D., Del Giudice, C., Ciccarelli, M., Franco, A., Crola, C., and Campiglia, P. (2015). Targeting the CaMKII\/ERK Interaction in the Heart Prevents Cardiac Hypertrophy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130477"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.yjmcc.2018.07.004","article-title":"Mitochondrial fission protein, dynamin-related protein 1, contributes to the promotion of hypertensive cardiac hypertrophy and fibrosis in Dahl-salt sensitive rats","volume":"121","author":"Hasan","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1152\/physiol.00029.2009","article-title":"The Roles of CaMKII and F-Actin in the Structural Plasticity of Dendritic Spines: A Potential Molecular Identity of a Synaptic Tag?","volume":"24","author":"Okamoto","year":"2009","journal-title":"Physiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.celrep.2018.06.011","article-title":"CaMKK2 Regulates Mechanosensitive Assembly of Contractile Actin Stress Fibers","volume":"24","author":"Tojkander","year":"2018","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1042\/CS20160312","article-title":"Novel role of Vav1-Rac1 pathway in actin cytoskeleton regulation in interleukin-13-induced minimal change-like nephropathy","volume":"130","author":"Chan","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ma, N., Xu, E., Luo, Q., and Song, G. (2023). Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy. Molecules, 28.","DOI":"10.3390\/molecules28072976"},{"key":"ref_38","unstructured":"McManus, L.M., and Mitchell, R.N. (2014). Pathobiology of Human Disease, Academic Press."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Fdez, S., Lorenzo-Mart\u00edn, L.F., Fabbiano, S., Menacho-M\u00e1rquez, M., Sauzeau, V., Dosil, M., and Bustelo, X.R. (2021). New Functions of Vav Family Proteins in Cardiovascular Biology, Skeletal Muscle, and the Nervous System. Biology, 10.","DOI":"10.3390\/biology10090857"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1161\/01.RES.0000216039.75913.9e","article-title":"The Rac and Rho Hall of Fame","volume":"98","author":"Brown","year":"2006","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1161\/HYPERTENSIONAHA.110.157784","article-title":"Novel Role of Rac1\/WAVE Signaling Mechanism in Regulation of the Epithelial Na+ Channel","volume":"57","author":"Karpushev","year":"2011","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/nri840","article-title":"VAV proteins as signal integrators for multi-subunit immune-recognition receptors","volume":"2","author":"Turner","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41420-022-00927-4","article-title":"Regulation of the Tec family of non-receptor tyrosine kinases in cardiovascular disease","volume":"8","author":"Yin","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"H713","DOI":"10.1152\/ajpheart.00273.2010","article-title":"Stress signaling by Tec tyrosine kinase in the ischemic myocardium","volume":"299","author":"Zhang","year":"2010","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.tcb.2003.07.001","article-title":"Tec kinases: Shaping T-cell activation through actin","volume":"14","author":"Finkelstein","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.2147\/OTT.S198542","article-title":"TPM4 promotes cell migration by modulating F-actin formation in lung cancer","volume":"12","author":"Zhao","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00001.2007","article-title":"Tropomyosin-based regulation of the actin cytoskeleton in time and space","volume":"88","author":"Gunning","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_48","unstructured":"Ozgur, K. (2018). Cardiac Diseases and Interventions in 21st Century, IntechOpen. Chapter 2."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1161\/01.HYP.0000050646.79785.7C","article-title":"Altered Tropomyosin Expression in Essential Hypertension","volume":"41","author":"Dunn","year":"2003","journal-title":"Hypertension"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1146\/annurev.pharmtox.40.1.617","article-title":"14-3-3 Proteins: Structure, Function, and Regulation","volume":"40","author":"Fu","year":"2000","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fasebj.2020.34.s1.08946","article-title":"Deduced Roles of Cardiac 14-3-3 Protein Interactome in Heart Metabolism, Protein Synthesis and Proteostasis","volume":"34","author":"Qu","year":"2020","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1016\/S0960-9822(02)01184-3","article-title":"14-3-3 Regulates Actin Dynamics by Stabilizing Phosphorylated Cofilin","volume":"12","author":"Gohla","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hajka, D., Budziak, B., Pietras, \u0141., Duda, P., McCubrey, J.A., and Gizak, A. (2021). GSK3 as a Regulator of Cytoskeleton Architecture: Consequences for Health and Disease. Cells, 10.","DOI":"10.3390\/cells10082092"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/med.21867","article-title":"Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases","volume":"42","author":"Wang","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1161\/CIRCRESAHA.107.160614","article-title":"Inhibition of Glycogen Synthase Kinase 3\u03b2 During Heart Failure Is Protective","volume":"101","author":"Hirotani","year":"2007","journal-title":"Circ. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1161\/CIRCRESAHA.116.303613","article-title":"The GSK-3 Family as Therapeutic Target for Myocardial Diseases","volume":"116","author":"Lal","year":"2015","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7354","DOI":"10.1038\/ncomms8354","article-title":"Grb2 monomer\u2013dimer equilibrium determines normal versus oncogenic function","volume":"6","author":"Ahmed","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21946","DOI":"10.1074\/jbc.M000687200","article-title":"GRB2 Links Signaling to Actin Assembly by Enhancing Interaction of Neural Wiskott-Aldrich Syndrome Protein (N-WASp) with Actin-related Protein (ARP2\/3) Complex","volume":"275","author":"Carlier","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.bbamcr.2016.12.011","article-title":"Myogenic differentiation depends on the interplay of Grb2 and N-WASP","volume":"1864","author":"Mitra","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1172\/JCI16290","article-title":"The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis","volume":"111","author":"Zhang","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1161\/01.ATV.0000085015.49110.85","article-title":"Grb2 Is Required for the Development of Neointima in Response to Vascular Injury","volume":"23","author":"Zhang","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, J., Sun, X., Wang, X., Cui, S., Liu, R., Liu, J., Fu, B., Gong, M., Wang, C., and Shi, Y. (2021). Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt\/mTOR Pathway. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.630412"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Al Kuwari, H., Al Thani, A., Al Marri, A., Al Kaabi, A., Abderrahim, H., Afifi, N., Qafoud, F., Chan, Q., Tzoulaki, I., and Downey, P. (2015). The Qatar Biobank: Background and methods. BMC Public Health, 15.","DOI":"10.1186\/s12889-015-2522-7"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1093\/aje\/kwz084","article-title":"Qatar Biobank Cohort Study: Study Design and First Results","volume":"188","author":"Fthenou","year":"2019","journal-title":"Am. J. Epidemiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jprot.2016.08.023","article-title":"Complementarity of SOMAscan to LC-MS\/MS and RNA-seq for quantitative profiling of human embryonic and mesenchymal stem cells","volume":"150","author":"Billing","year":"2017","journal-title":"J. Proteom."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14357","DOI":"10.1038\/ncomms14357","article-title":"Connecting genetic risk to disease end points through the human blood plasma proteome","volume":"8","author":"Suhre","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/hmg\/ddac243","article-title":"Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations","volume":"32","author":"Thareja","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4896\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:37:12Z","timestamp":1760107032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25094896"],"URL":"https:\/\/doi.org\/10.3390\/ijms25094896","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,30]]}}}