Next Article in Journal
Optimal Timing of External Ventricular Drainage after Severe Traumatic Brain Injury: A Systematic Review
Previous Article in Journal
Outcome of Root Canal Treatments Provided by Endodontic Postgraduate Students. A Retrospective Study
Open AccessReview

Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets

1
Department of Biomedicine and Prevention, Anatomic Pathology Institute, Tor Vergata University of Rome, 00133 Rome, Italy
2
Department of Surgical Sciences, Plastic and Reconstructive Surgery, Tor Vergata University of Rome, 00133 Rome, Italy
3
Biomedical Sciences Department, Calixto García Faculty, University of Medical Sciences of Havana, Havana 11600, Cuba
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(6), 1995; https://doi.org/10.3390/jcm9061995
Received: 7 May 2020 / Revised: 15 June 2020 / Accepted: 23 June 2020 / Published: 25 June 2020
(This article belongs to the Section Vascular Medicine)
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. View Full-Text
Keywords: cardiovascular diseases; endothelial dysfunction; oxidative stress; biomarkers; therapeutic targets cardiovascular diseases; endothelial dysfunction; oxidative stress; biomarkers; therapeutic targets
Show Figures

Figure 1

MDPI and ACS Style

Scioli, M.G.; Storti, G.; D’Amico, F.; Rodríguez Guzmán, R.; Centofanti, F.; Doldo, E.; Céspedes Miranda, E.M.; Orlandi, A. Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets. J. Clin. Med. 2020, 9, 1995.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop