Oxidative Stress and Reactive Oxygen Species in Cardiovascular Disease

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 1786

Special Issue Editors

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Guest Editor
Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Interests: platelet activation; oxidative stress; inflammation
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Special Issue Information

Dear Colleagues,

Cardiovascular disease (CVD) is the leading cause of mortality and the most expensive health condition worldwide. Pre-clinical and clinical studies associated the imbalance of oxidative stress and antioxidant status with the pathogenesis of CVD. Thus, upregulation of reactive oxygen species (ROS)-producing enzymes such as NADPH oxidase, along with downregulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occurs during CVD development. This imbalance may predispose to athero-thrombosis by enhancing platelet and clotting activation and inducing endothelial dysfunction.

Recently, gut-derived products, such as trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS), are emerging as novel cardiovascular risk factors. In particular, LPS is a pro-atherogenic molecule through its pro-oxidant properties, which are mediated by NOX2 activation, one of the most important cellular producers of ROS. LPS may translocate into systemic circulation upon microbiota dysbiosis-induced gut barrier dysfunction and can amplify platelet responses via Toll-like receptor 4 (TLR4) activation and NOX2-derived ROS formation. Another mechanism involved in maintaining redox balance is autophagy which is a crucial adaptive cellular response to oxidative stress, removing excessive cellular ROS; in fact, recent evidence showed that oxidative stress Nox2-mediated is associated with autophagy inhibition. Furthermore, autophagy preserves endothelial function through attenuation of ROS production and inflammatory signaling and increasing nitric oxide (NO) bioavailability.

Reducing oxidative stress represents a promising approach to the prevention and treatment of CVD. Therefore, the identification of strategies targeted to modulate redox balance, by activation or inhibition of specific enzymatic sources of ROS, improvement of gut microbiota and permeability, or potentiating pro-autophagic effects, is necessary.

This Special Issue will focus on the causes and consequences of oxidative stress in CVD exploring cellular and molecular mechanisms involved and emerging treatment strategies.

Dr. Roberto Carnevale
Dr. Vittoria Cammisotto
Guest Editors

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  • oxidative stress, reactive oxygen species
  • cardiovascular disease, cardiovascular risk factor
  • oxidative stress biomarkers, redox signaling
  • platelet activation and oxidative stress
  • endothelial dysfunction and oxidative stress
  • dysbiosis and oxidative stress
  • autophagy and oxidative stress
  • antioxidant therapy

Published Papers (1 paper)

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15 pages, 4236 KiB  
C2CD4B Evokes Oxidative Stress and Vascular Dysfunction via a PI3K/Akt/PKCα–Signaling Pathway
by Paola Di Pietro, Angela Carmelita Abate, Valeria Prete, Antonio Damato, Eleonora Venturini, Maria Rosaria Rusciano, Carmine Izzo, Valeria Visco, Michele Ciccarelli, Carmine Vecchione and Albino Carrizzo
Antioxidants 2024, 13(1), 101; https://doi.org/10.3390/antiox13010101 - 14 Jan 2024
Viewed by 1375
High glucose–induced endothelial dysfunction is an important pathological feature of diabetic vasculopathy. While genome-wide studies have identified an association between type 2 diabetes mellitus (T2DM) and increased expression of a C2 calcium-dependent domain containing 4B (C2CD4B), no study has yet explored the possible [...] Read more.
High glucose–induced endothelial dysfunction is an important pathological feature of diabetic vasculopathy. While genome-wide studies have identified an association between type 2 diabetes mellitus (T2DM) and increased expression of a C2 calcium-dependent domain containing 4B (C2CD4B), no study has yet explored the possible direct effect of C2CD4B on vascular function. Vascular reactivity studies were conducted using a pressure myograph, and nitric oxide and oxidative stress were assessed through difluorofluorescein diacetate and dihydroethidium, respectively. We demonstrate that high glucose upregulated both mRNA and protein expression of C2CD4B in mice mesenteric arteries in a time-dependent manner. Notably, the inhibition of C2CD4B expression by genetic knockdown efficiently prevented hyperglycemia–induced oxidative stress, endothelial dysfunction, and loss of nitric oxide (NO) bioavailability. Recombinant C2CD4B evoked endothelial dysfunction of mice mesenteric arteries, an effect associated with increased reactive oxygen species (ROS) and decreased NO production. In isolated human umbilical vein endothelial cells (HUVECs), C2CD4B increased phosphorylation of endothelial nitric oxide synthase (eNOS) at the inhibitory site Thr495 and reduced eNOS dimerization. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and PKCα effectively attenuated oxidative stress, NO reduction, impairment of endothelial function, and eNOS uncoupling induced by C2CD4B. These data demonstrate, for the first time, that C2CD4B exerts a direct effect on vascular endothelium via a phosphoinositide 3-kinase (PI3K)/Akt/PKCα–signaling pathway, providing a new perspective on C2CD4B as a promising therapeutic target for the prevention of oxidative stress in diabetes–induced endothelial dysfunction. Full article
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