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Activation of Nrf2/HO-1 Pathway and Human Atherosclerotic Plaque Vulnerability:an In Vitro and In Vivo Study.
- Source :
-
Cells [Cells] 2019 Apr 16; Vol. 8 (4). Date of Electronic Publication: 2019 Apr 16. - Publication Year :
- 2019
-
Abstract
- Reactive oxygen species (ROS) induce nuclear factor erythroid 2-related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque.<br />Competing Interests: Funding: This work was supported by the Italian Ministry of Health, Rome, Italy (Ricerca Corrente 2014: CC13; 2015: CC13; 2016: CC18). Co-funding provided by the contribution of the Italian “5 × 1000” tax (2010, 2011, 2012).
- Subjects :
- Aged
Female
Humans
Male
Middle Aged
Antioxidants metabolism
Atherosclerosis metabolism
Coronary Artery Disease metabolism
Coronary Artery Disease physiopathology
Macrophages metabolism
Macrophages physiology
Membrane Proteins genetics
Oxidative Stress physiology
Reactive Oxygen Species metabolism
Signal Transduction
Tomography, Optical Coherence methods
Heme Oxygenase-1 genetics
Heme Oxygenase-1 metabolism
Heme Oxygenase-1 physiology
NF-E2-Related Factor 2 genetics
NF-E2-Related Factor 2 metabolism
NF-E2-Related Factor 2 physiology
Plaque, Atherosclerotic metabolism
Plaque, Atherosclerotic physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 30995787
- Full Text :
- https://doi.org/10.3390/cells8040356