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Published on: August 17, 2022
Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and
Maria Giovanna Scioli1, Gabriele Storti2, Federico D'Amico1
1Department of Biomedicine and Prevention, Anatomic Pathology Institute, Tor Vergata University of Rome, 00133 Rome, Italy.
Insights
Cardiovascular diseases are a leading cause of death, often driven by endothelial dysfunction and oxidative stress. New therapies targeting these mechanisms show promise for prevention and treatment.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Molecular Biology
Background:
- Cardiovascular diseases (CVD) are the primary global cause of death and illness.
- Endothelial dysfunction, characterized by reduced nitric oxide and inflammation, is central to CVD pathogenesis.
- Oxidative stress, particularly mitochondrial reactive oxygen species (ROS), exacerbates endothelial dysfunction and promotes apoptosis.
Purpose of the Study:
- To explore the role of oxidative stress and inflammation in endothelial dysfunction related to CVD.
- To identify novel biomarkers for endothelial dysfunction in CVD.
- To review current and emerging therapeutic strategies for endothelial dysfunction.
Main Methods:
- Literature review of studies on endothelial dysfunction, oxidative stress, and CVD.
- Analysis of molecular mechanisms including ROS production, cardiolipin oxidation, and cytochrome-c release.
- Examination of therapeutic approaches such as gene therapy and enzyme inhibitors.
Main Results:
- Endothelial dysfunction involves increased adhesion molecules, leukocyte adherence, and vascular smooth muscle cell proliferation.
- Mitochondrial ROS contribute to macromolecular oxidation, apoptosis, and altered endothelial signaling.
- Current therapies like carriers and gene therapy show clinical utility, with ongoing research into personalized treatments.
Conclusions:
- Identifying new oxidative stress markers is crucial for CVD prevention and therapy.
- Advanced therapeutic strategies, including gene therapy and stabilizers, offer potential for managing endothelial dysfunction.
- Further research is needed to overcome challenges in implementing personalized treatments for CVD.
Abstract:
Cardiovascular diseases (CVD), including heart and pathological circulatory conditions, are the world's leading cause of mortality and morbidity. Endothelial dysfunction involved in CVD pathogenesis is a trigger, or consequence, of oxidative stress and inflammation. Endothelial dysfunction is defined as a diminished production/availability of nitric oxide, with or without an imbalance between endothelium-derived contracting, and relaxing factors associated with a pro-inflammatory and prothrombotic status. Endothelial dysfunction-induced phenotypic changes include up-regulated expression of adhesion molecules and increased chemokine secretion, leukocyte adherence, cell permeability, low-density lipoprotein oxidation, platelet activation, and vascular smooth muscle cell proliferation and migration. Inflammation-induced oxidative stress results in an increased accumulation of reactive oxygen species (ROS), mainly derived from mitochondria. Excessive ROS production causes oxidation of macromolecules inducing cell apoptosis mediated by cytochrome-c release. Oxidation of mitochondrial cardiolipin loosens cytochrome-c binding, thus, favoring its cytosolic release and activation of the apoptotic cascade. Oxidative stress increases vascular permeability, promotes leukocyte adhesion, and induces alterations in endothelial signal transduction and redox-regulated transcription factors. Identification of new endothelial dysfunction-related oxidative stress markers represents a research goal for better prevention and therapy of CVD. New-generation therapeutic approaches based on carriers, gene therapy, cardiolipin stabilizer, and enzyme inhibitors have proved useful in clinical practice to counteract endothelial dysfunction. Experimental studies are in continuous development to discover new personalized treatments. Gene regulatory mechanisms, implicated in endothelial dysfunction, represent potential new targets for developing drugs able to prevent and counteract CVD-related endothelial dysfunction. Nevertheless, many challenges remain to overcome before these technologies and personalized therapeutic strategies can be used in CVD management.
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