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Internal and Emergency Medicine

, Volume 13, Issue 5, pp 647–649 | Cite as

Oxidative stress and inflammation: new molecular targets for cardiovascular diseases

  • Matteo BecattiEmail author
  • Amanda Mannucci
  • Niccolò Taddei
  • Claudia Fiorillo
IM - COMMENTARY

Coronary artery disease (CAD) is the underlying condition in most acute coronary events and the leading cause of death in developed countries [1]. The previous studies have shown that oxidative stress, a condition caused by an imbalance between reactive oxygen species (ROS) production and antioxidant defense systems and closely associated with many other chronic and acute disorders [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12], contributes to the initiation and progression of endothelial dysfunction and atherogenesis [13]. Indeed, ROS can damage every cell component, such as lipids, proteins, and DNA, and can also trigger pro-inflammatory cytokine production.

In many pathogenetic events of atherosclerosis such as endothelial dysfunction, low-density lipoprotein oxidation (OxLDL) [14], vascular smooth muscle cell proliferation, platelet aggregation and inflammation, and ROS, may play pivotal roles [15].

Inflammation-induced endothelial injury emerges as a key factor connecting chronic inflammation and thrombosis [16, 17]. However, its pathogenic mechanisms still remain a matter of debate. Many studies support oxidative stress and inflammation as interconnected processes that co-exist in the inflamed milieu [16, 17, 18]. ROS are released by inflammatory cells at the site of inflammation leading to oxidative damage; on the other hand, ROS production enhances pro-inflammatory responses. In the earliest phases of atherogenesis, neutrophils are recruited by the dysfunctional endothelial surface, where they increase ROS production and invade the vessel wall. After extravasation, neutrophils sustain a vicious cycle leading to chronic inflammation and increased plaque vulnerability by releasing oxidative enzymes, ROS, and chemokines [18].

Neutrophil extracellular traps (NETs) have been identified in 2004 as a new neutrophil pathogen-killing mechanism, and have been proven beneficial against infections [19]. NETs are extracellular DNA fibers comprising histones and neutrophil antimicrobial proteins. Extracellular DNA traps are also observed in inflammatory but noninfectious diseases, like autoimmune diseases [20] or psoriasis [21]. New emerging data describe NETs as the key players of several vascular diseases, such as acute coronary syndrome, stroke, venous thrombosis, and atherosclerosis [22]. Indeed, NETs have been identified within atherosclerotic lesions and arterial thrombi in both human beings and animal models [17].

In line with these observations, our recent findings demonstrate the key role of neutrophil-derived ROS in thrombus formation in Behçet disease (BD) patients (a model of inflammation-induced thrombosis), supporting current concepts regarding the link between inflammation, oxidative stress, and thrombosis [17].

This issue of the IAEM includes interesting research by Mozzini et al. [23] who outline new insights on the multiple and apparently contradictory facets of nuclear factor kappa B (NF-κB) in unstable angina (UA) and on its possible mediator role in NETs formation. NF-κB is a major transcription factor involved in the inflammatory cascade [24]. Studies show a strong association between NF-κB activation and development of heart failure in both human and animal models [25, 26]. It has been reported that NF-κB is involved in the process of venous thrombosis [27], and can regulate the expression of tissue factor, which plays a crucial role in the initiation of the coagulation cascade by regulating p50/p65 heterodimer [28]. However, the role of NF-κB in NETs formation is not completely understood.

Mozzini et al. investigated the role of NF-Kb in 23 patients with UA free of symptoms after a year follow-up (UA1YFU). They assessed several oxidative stress and inflammation blood markers, describing an improvement of the inflammatory status in patients with a history of UA. In particular, they show significantly decreased levels of NF-kB, plasma oxidized low-density lipoproteins (ox-LDL), high-sensitivity C-reactive protein (hs-CRP), and double-stranded DNA (ds-DNA) plasma levels in UA1YFU patients compared to UA at baseline but not vs stable angina (SA) patients. Furthermore, among pro-inflammatory cytokines, IL-6 levels in UA1YFU patients are lower than in UA at baseline, but significantly higher if compared to SA. In contrast, IL-1β levels in UA1YFU patients are lower than UA at baseline, and no differences are found if compared to SA. According to recent literature, data by Mozzini and co-workers report an interesting link among cytokines, NF-κB, and NETs in UA after 1 year of follow-up. The reported results indicate an improvement of inflammatory conditions after 1 year follow-up of UA patients.

Based on these results, we think that a better understanding of the molecular pathways connecting inflammation and oxidative stress will open the door to new therapeutic targets for cardiovascular diseases.

Notes

Compliance with ethical standards

Conflict of interest

None.

Statements on human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

None.

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Copyright information

© SIMI 2018

Authors and Affiliations

  1. 1.Department of Experimental and Clinical Biomedical Sciences “Mario Serio”University of FlorenceFlorenceItaly

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