HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature
Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2025-01-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL27004 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586532380213248 |
|---|---|
| author | Dimitra P. Vageli Panagiotis G. Doukas Dimitrios Georgiou Michailangelos P. Prokopiou Nefeli E. Ladaki Androniki Papadopoulou Sotirios G. Doukas Konstantina Zacharouli Konstantinos P. Makaritsis Maria Ioannou |
| author_facet | Dimitra P. Vageli Panagiotis G. Doukas Dimitrios Georgiou Michailangelos P. Prokopiou Nefeli E. Ladaki Androniki Papadopoulou Sotirios G. Doukas Konstantina Zacharouli Konstantinos P. Makaritsis Maria Ioannou |
| author_sort | Dimitra P. Vageli |
| collection | DOAJ |
| description | Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy. Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis. We used the terms {“Atherosclerosis” [OR] “Atheroma” [OR] “atheromatous plaque” [OR] “plaque atherosclerotic”} [AND] {“HIF-1α”} [AND] {“VEGF”} from 2009 up to May 2024 and the Medline/Embase/PubMed database. We used methodological approaches to assess unbiased data [ROBIS (Risk of Bias in Systematic) tool]. We used study eligibility criteria, and data were collected and evaluated from original articles by two independent teams, judged by an independent reviewer, and reported by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020. Results: We included 34 original studies investigating 650 human specimens, 21 different cell lines, and 9 animal models. Increased HIF-1α in vascular smooth muscle cells, macrophages, or endothelial cells, under hypoxia, chronic loss of nitric oxide (NO), or reduced micro ribonucleic acid (miRNA)-17 and miR-20, is associated with the upregulation of pro-inflammatory molecules, such as interleukin-1 beta (IL-1β) or tumor necrosis factor-alpha (TNF-α), increased migration inhibitory factor of macrophages, glycolytic flux, lipid accumulation, necroptosis via miR-383, and adverse effects in atherosclerosis and plaque vulnerability. However, increased HIF-1α in lymphocytes is associated with decreased interferon-gamma (IFN-γ) and a favorable prognosis. Increased VEGF in a coronary artery, activated macrophages, or chronic exposure to methamphetamine is associated with elevated levels of serum inflammatory cells (interleukin-18; IL18), p38 mitogen-activated protein kinase (MAPK) phosphorylation, lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), and signal transducer and activator of transcription 6 isoform B (STAT6B) overexpression, leading to atherosclerosis progression and plaque break. However, VEGF overexpression in serum is marginally associated with an elevated risk for atherosclerosis. In contrast, stable overexpression of VEGF in macrophages correlates with reduced hyperplasia after arterial injury, reduced foam cell formation, and attenuation of atherosclerosis progression. HIF-1α/VEGF immunophenotypes reflect atherosclerosis treatment efficacy using, among others, HIF-inhibitors, statins, polyphenols, miR-497-5p, methylation modification, adenosine receptor antagonists, natural products, or glycosides. Conclusion: We present an overview of HIF-1α/VEGF expression in chronic inflammatory-related atherosclerosis disease. Exploring pathogenetic mechanisms and therapeutic options, we included several studies using variable methods to evaluate HIF-1α/VEGF immunophenotypes with controversial and innovative results. Data limitations may include the use of different survival methods. Our data support HIF-1α/VEGF immunophenotypes as potential biomarkers of atherosclerosis prognosis and treatment efficacy. |
| format | Article |
| id | doaj-art-bea0488b744e4632ae936775a8df03c2 |
| institution | Kabale University |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-bea0488b744e4632ae936775a8df03c22025-01-25T08:55:52ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-01-013012700410.31083/FBL27004S2768-6701(24)01562-4HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the LiteratureDimitra P. Vageli0Panagiotis G. Doukas1Dimitrios Georgiou2Michailangelos P. Prokopiou3Nefeli E. Ladaki4Androniki Papadopoulou5Sotirios G. Doukas6Konstantina Zacharouli7Konstantinos P. Makaritsis8Maria Ioannou9Department of Neurology, Neuroscience and Regeneration Research Center Yale University School of Medicine & VA-CT, West Haven, CT 06516, USADepartment of Medicine, Rutgers-Robert Wood Johnson Medical School/Saint Peter's University Hospital, New Brunswick, NJ 08901, USADepartment of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, GreeceDepartment of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, GreeceDepartment of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, GreeceDepartment of Anesthesiology, G. Gennimatas General Hospital, 54635 Thessaloniki, GreeceDepartment of Medicine, Section of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School/Saint Peter's University Hospital, New Brunswick, NJ 08901, USADepartment of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, GreeceDepartment of Medicine & Research Laboratory of Internal Medicine, Faculty of Medicine, University of Thessaly/National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, GreeceDepartment of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, GreeceBackground: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy. Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis. We used the terms {“Atherosclerosis” [OR] “Atheroma” [OR] “atheromatous plaque” [OR] “plaque atherosclerotic”} [AND] {“HIF-1α”} [AND] {“VEGF”} from 2009 up to May 2024 and the Medline/Embase/PubMed database. We used methodological approaches to assess unbiased data [ROBIS (Risk of Bias in Systematic) tool]. We used study eligibility criteria, and data were collected and evaluated from original articles by two independent teams, judged by an independent reviewer, and reported by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020. Results: We included 34 original studies investigating 650 human specimens, 21 different cell lines, and 9 animal models. Increased HIF-1α in vascular smooth muscle cells, macrophages, or endothelial cells, under hypoxia, chronic loss of nitric oxide (NO), or reduced micro ribonucleic acid (miRNA)-17 and miR-20, is associated with the upregulation of pro-inflammatory molecules, such as interleukin-1 beta (IL-1β) or tumor necrosis factor-alpha (TNF-α), increased migration inhibitory factor of macrophages, glycolytic flux, lipid accumulation, necroptosis via miR-383, and adverse effects in atherosclerosis and plaque vulnerability. However, increased HIF-1α in lymphocytes is associated with decreased interferon-gamma (IFN-γ) and a favorable prognosis. Increased VEGF in a coronary artery, activated macrophages, or chronic exposure to methamphetamine is associated with elevated levels of serum inflammatory cells (interleukin-18; IL18), p38 mitogen-activated protein kinase (MAPK) phosphorylation, lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), and signal transducer and activator of transcription 6 isoform B (STAT6B) overexpression, leading to atherosclerosis progression and plaque break. However, VEGF overexpression in serum is marginally associated with an elevated risk for atherosclerosis. In contrast, stable overexpression of VEGF in macrophages correlates with reduced hyperplasia after arterial injury, reduced foam cell formation, and attenuation of atherosclerosis progression. HIF-1α/VEGF immunophenotypes reflect atherosclerosis treatment efficacy using, among others, HIF-inhibitors, statins, polyphenols, miR-497-5p, methylation modification, adenosine receptor antagonists, natural products, or glycosides. Conclusion: We present an overview of HIF-1α/VEGF expression in chronic inflammatory-related atherosclerosis disease. Exploring pathogenetic mechanisms and therapeutic options, we included several studies using variable methods to evaluate HIF-1α/VEGF immunophenotypes with controversial and innovative results. Data limitations may include the use of different survival methods. Our data support HIF-1α/VEGF immunophenotypes as potential biomarkers of atherosclerosis prognosis and treatment efficacy.https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL27004hif-1αvegfimmunoassaysatherosclerosisachromatic plaquehypoxiaangiogenesisatherosclerosis prognosisatherosclerosis targeted therapy |
| spellingShingle | Dimitra P. Vageli Panagiotis G. Doukas Dimitrios Georgiou Michailangelos P. Prokopiou Nefeli E. Ladaki Androniki Papadopoulou Sotirios G. Doukas Konstantina Zacharouli Konstantinos P. Makaritsis Maria Ioannou HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature Frontiers in Bioscience-Landmark hif-1α vegf immunoassays atherosclerosis achromatic plaque hypoxia angiogenesis atherosclerosis prognosis atherosclerosis targeted therapy |
| title | HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature |
| title_full | HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature |
| title_fullStr | HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature |
| title_full_unstemmed | HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature |
| title_short | HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature |
| title_sort | hif 1α and vegf immunophenotypes as potential biomarkers in the prognosis and evaluation of treatment efficacy of atherosclerosis a systematic review of the literature |
| topic | hif-1α vegf immunoassays atherosclerosis achromatic plaque hypoxia angiogenesis atherosclerosis prognosis atherosclerosis targeted therapy |
| url | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL27004 |
| work_keys_str_mv | AT dimitrapvageli hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT panagiotisgdoukas hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT dimitriosgeorgiou hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT michailangelospprokopiou hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT nefelieladaki hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT andronikipapadopoulou hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT sotiriosgdoukas hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT konstantinazacharouli hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT konstantinospmakaritsis hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature AT mariaioannou hif1aandvegfimmunophenotypesaspotentialbiomarkersintheprognosisandevaluationoftreatmentefficacyofatherosclerosisasystematicreviewoftheliterature |