Linking oxidative stress biomarkers to disease progression and antioxidant therapy in hypertension and diabetes mellitus
Open accessAbstract
Oxidative stress (OS) is increasingly recognized as a key factor linking hypertension (HTN) and diabetes mellitus (DM). This review summarizes recent evidence regarding the dual role of OS as both an instigator and an amplifier of cardiometabolic dysfunction. In HTN, reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) and mitochondrial dysfunction contribute to endothelial impairment and vascular remodeling. In DM, hyperglycemia-induced ROS production worsens beta-cell failure and insulin resistance through pathways such as the AGE-RAGE signaling, protein kinase C (PKC) activation, and the polyol pathway. Clinically validated biomarkers of OS, such as F2-isoprostanes (which indicate lipid peroxidation), 8-OHdG (which indicates DNA damage), and the activities of redox enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx), show strong correlations with disease progression and end-organ complications. Despite promising preclinical results, the application of antioxidant therapies in clinical settings has faced challenges due to inconsistent outcomes, highlighting the need for targeted approaches. Emerging strategies include: 1. Mitochondria-targeted antioxidants to enhance vascular function in resistant HTN; 2. Nrf2 activators to restore redox balance in early diabetes; and 3. Specific inhibitors of NOX isoforms. We emphasize three transformative areas of research: (i) the interaction between the microbiome and ROS, where modifying gut microbiota can reduce systemic OS; (ii) the use of nanotechnology to deliver antioxidants directly to pancreatic islets or atherosclerotic plaques; and (iii) phenotype-specific diagnosis and therapy guided by redox biomarkers and genetic profiling (for example, KEAP1/NRF2 polymorphisms). Integrating these advances with lifestyle modifications, such as following a Mediterranean diet and exercising regularly, may provide additional benefits. This review outlines a mechanistic framework for targeting OS in the comorbidity of HTN and DM while identifying critical knowledge gaps, particularly regarding the timing of antioxidant signaling and the development of personalized redox medicine, which may serve as a reference for researchers and clinicians working in this area.
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The present evidence base for lipid peroxidation markers remains heterogeneous in marker selection, assay platform, and standardization, and direct comparative evidence against standard clinic-based models is still limited.
“This supports the idea that lipid peroxidation markers may serve as mechanistically plausible candidate predictors; however, the present evidence base remains heterogeneous in marker selection, assay platform, and standardization, and direct comparative evidence against standard clinic-based models is still limited (20–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
The Introduction (page unavailable) says biomarker variability and a lack of standardized assays limit clinical adoption. Section 3 (page unavailable) identifies different lipid-peroxidation markers and assay platforms, and Section 7 notes biases from independently applied methods. The paper does not establish that direct comparisons with standard clinic-based prediction models are limited. (LLM, conf=0.85)
Experimental — accuracy not yet measuredLipid peroxidation markers may serve as mechanistically plausible candidate predictors for cardiovascular complications in diabetes.
“This supports the idea that lipid peroxidation markers may serve as mechanistically plausible candidate predictors; however, the present evidence base remains heterogeneous in marker selection, assay platform, and standardization, and direct comparative evidence against standard clinic-based models is still limited (20–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
Oxidative stress plays a central role in the shared pathophysiology of diabetes and cardiovascular disease, with lipid peroxidation representing one of its major downstream consequences.
“Oxidative stress plays a central role in the shared pathophysiology of diabetes and cardiovascular disease, with lipid peroxidation representing one of its major downstream consequences.”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
Oxidized lipid products and related oxidative stress markers may reflect vascular injury, inflammatory activity, and cardiometabolic dysfunction.
“Studies have shown that oxidized lipid products and related oxidative stress markers may reflect vascular injury, inflammatory activity, and cardiometabolic dysfunction (18–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
Integrating mechanistic biomarkers such as those related to lipid peroxidation holds potential to improve biological relevance and possibly predictive performance.
“Moreover, integrating mechanistic biomarkers—such as those related to lipid peroxidation—holds potential to improve biological relevance and possibly predictive performance (18–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
The association between lipid peroxidation and diabetic cardiovascular complications has been extensively discussed in the literature.
“The association between lipid peroxidation and diabetic cardiovascular complications has been extensively discussed in the literature (18, 19, 21, 22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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Oxidative Stress Biomarkers in Hypertension
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Crumbling Pathogenesis and Biomarkers for Diabetic Peripheral Neuropathy
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Moderate‐Intensity Exercise Maintains Redox Homeostasis for Cardiovascular Health
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Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase
Greenberger, J. S., Mukherjee, A., & Epperly, M. W. (2021) · Antioxidants · doi:10.3390/antiox10071057 · Cited by 13 · see citing works
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Insulin Resistance in Type 2 Diabetes
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Novel NADPH Oxidase-2 Inhibitors as Potential Anti-Inflammatory and Neuroprotective Agents
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Molecular mechanisms involved in hyperglycemia-induced cellular damage
Pardina, E., Tondo, M., Escolá‐Gil, J. C., Rossell, J., & Julve, J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-88426-6.00012-9 · Cited by 12 · see citing works
Mass Spectrometry in Advancement of Redox Precision Medicine
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- Authors
- Nuñez-Selles, A. J., Nuñez-Musa, R. A., & Guillen-Marmolejos, R. A.
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2025-05-26
- Volume
- 12
- Pages
- 1611842-1611842
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC12146192
- OpenAlex
- W4410729041
- Cited by
- 51
- References
- 239
- Citations by year
- 2026: 42 · 2025: 9
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondo Nacional de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- oxidative stress, hypertension, diabetes mellitus, antioxidant therapy, reactive oxygen species, NADPH oxidase, mitochondrial dysfunction, endothelial dysfunction, vascular remodeling, hyperglycemia, beta-cell failure, insulin resistance, AGE-RAGE signaling pathway, polyol pathway, protein kinase C, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, glutathione peroxidase, Nrf2, gut microbiota, mitochondria-targeted antioxidants, NOX inhibitors, Mediterranean diet, physical activity, cardiometabolic dysfunction
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