| 1. |
- Cotoi, Ovidiu, et al.
(författare)
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Plasma procalcitonin is associated with all-cause and cancer mortality in apparently healthy men: a prospective population-based study.
- 2013
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovascular disease or cancer.
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| 2. |
- Cotoi, Ovidiu, et al.
(författare)
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Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals.
- 2014
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 34:1, s. 202-202
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Tidskriftsartikel (refereegranskat)abstract
- The S100 alarmins A8, A9, and A8/A9, secreted by activated neutrophils and monocytes/macrophages, are involved in the pathogenesis of various inflammatory diseases. S100A8/A9 has previously been linked to atherogenesis and cardiovascular (CV) disease. We investigated whether S100A8, A9, and A8/A9 correlate with carotid artery disease and CV risk in apparently healthy individuals.
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| 3. |
- Mares, Razvan Gheorghita, et al.
(författare)
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Innate immune mechanisms in myocardial infarction - An update
- 2018
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Ingår i: Revista Romana de Medicina de Laborator. - : Walter de Gruyter GmbH. - 1841-6624 .- 2284-5623. ; 26:1, s. 9-20
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Forskningsöversikt (refereegranskat)abstract
- Acute myocardial infarction (AMI) is a disease associated with high morbidity and mortality. Currently there are no available treatments specifically targeting the post-ischemic myocardial processes that lead to heart failure and recurrent coronary events. The innate immune system plays a central role in the two consecutive phases that follow an acute ischemic event: the inflammatory phase and the reparatory phase. The inflamatory phase involves a massive infiltration of neutrophils and inflammatory Ly6Chi monocytes into the injured myocardium. The reparatory phase is orchestrated by reparatory Ly6Clo macrophages that clear necrotic and apoptotic cells through efferocytosis, secrete anti-inflammatory mediators and stimulate fibrosis and repair. Important recent studies provided proof that Ly6Chi monocytes that enter the myocardium in the inflammatory phase upregulate the orphan nuclear receptor Nr4a1 and switch phenotype to Ly6CloNr4a1hi reparatory macrophages. Additionally, neutrophils have been shown to promote cardiac recovery by upregulating expression of the efferocytosis receptor MerTK on reparatory macrophages. A finely tuned balance between the inflammatory and the reparatory phases is thus essential for limiting myocardial damage and promoting efficient recovery. Treatment strategies targeting only the inflammatory phase have so far failed to improve prognosis in AMI patients. A detailed understanding of the interplay between the two phases of the innate immune response is paramount for designing efficient therapies able to improve post- AMI prognosis. In the current review, we summarize the state-of-the-art of the field and discuss previous therapeutic attempts and currently ongoing clinical trials targeting innate immune mechanisms in AMI patients.
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| 4. |
- Mareş, Răzvan Gheorghiţă, et al.
(författare)
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S100A8/A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction
- 2023
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Ingår i: Romanian Journal of Morphology and Embryology. - 1220-0522. ; 64:2, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8/A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8/A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8/A9 blockade on myocardial inflammation and post-ischemic myocardial injury in a mouse model of coronary artery ligation. Immunohistochemical (IHC) staining revealed that the presence of S100A9 is strongly correlated with neutrophil infiltration in the myocardium on days 1 and 3 post-MI. A 3-day treatment with the S100A8/A9 blocker ABR-238901 starting immediately after MI decreased the number of neutrophils and S100A9 presence in the myocardium and had a positive impact on cardiac damage, reducing infarction size. These findings promote S100A9 as an IHC biomarker of neutrophil infiltration and a promising immunomodulatory target to regulate neutrophil recruitment, reduce ischemic injury and promote long-term beneficial cardiac recovery after MI.
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| 5. |
- Mares, Razvan Gheorghita, et al.
(författare)
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Studying the innate immune response to myocardial infarction in a highly efficient experimental animal model
- 2021
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Ingår i: Revista Romana de Cardiologie. - : Walter de Gruyter GmbH. - 1220-658X. ; 31:3, s. 573-585
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Tidskriftsartikel (refereegranskat)abstract
- The reduction in mortality following acute myocardial infarction (AMI) is an important achievement of modern medicine. Despite this progress, AMI remains the most common cause of heart failure (HF) and HF-related morbidity and mortality. The involvement of the innate immune response in different stages after AMI has attracted important attention in recent years. With the increasing range of potential therapeutic compounds and delivery vectors, the need of highly efficient experimental AMI models is increasing, to support further advancement in this field. Here, we present a high-throughput model for the assessment of the innate immune response to AMI. The model is based on permanent surgical ligation of the left descending coronary artery (LAD) in mice, followed by complex flow-cytometry and histological analyses of immune cellular populations in blood and myocardium. We are presenting time-dependent qualitative and quantitative analysis results, demonstrating intense accumulation of Ly6Ghi neutrophils and Ly6Chi monocytes in the infarcted myocardium on days 1 and 3 post-AMI, followed by successive accumulation of reparatory Ly6CloMerTKhi macrophages, neovascularization and fibrosis development by day 7.
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| 6. |
- Schiopu, Alexandru, et al.
(författare)
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Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
- 2012
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 223:2, s. 291-298
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Transplant arteriosclerosis (TA) restricts long-term survival of heart transplant recipients. Although the role of monocyte/macrophages is well established in native atherosclerosis, it has been studied to a much lesser extent in TA. Plasma cholesterol is the most important non-immunologic risk factor for development of TA but the underlying mechanisms are largely unknown. We hypothesized that monocyte/macrophages might play an important role in the pathogenesis of TA under hyperlipidemic conditions. Methods: We studied TA in fully mismatched arterial allografts transplanted into hyperlipidemic ApoE(-/-) recipients compared to wild-type controls. The recruitment of distinct monocyte populations into the grafts was tracked by in vivo labelling with fluorescent microspheres. We used antibody-mediated depletion protocols to dissect the relative contribution of T lymphocytes and monocytes to disease development. Results: In the hyperlipidemic environment the progression of TA was highly exacerbated and the inflammatory CD11b(+)CD115(+)Ly-6C(hi) monocytes were preferentially recruited into the neointima. The number of macrophage-derived foam cells present in the grafts strongly correlated with plasma cholesterol and disease severity. Depletion of Ly-6C(hi) monocytes and neutrophils significantly inhibited macrophage accumulation and disease progression. The accelerated monocyte recruitment occurs through a T cell-independent mechanism, as T cell depletion did not influence macrophage accumulation into the grafts. Conclusions: Our study identifies for the first time the involvement of inflammatory Ly-6C(hi) monocytes into the pathogenesis of TA, particularly in conditions of hyperlipidemia. Targeted therapies modulating the recruitment and activation of these cells could potentially delay coronary allograft vasculopathy and improve long-term survival of heart transplant recipients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 7. |
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| 8. |
- Schiopu, Alexandru, et al.
(författare)
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S100A8 and S100A9: DAMPs at the crossroads between innate immunity, traditional risk factors, and cardiovascular disease.
- 2013
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2013:Dec 22
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Forskningsöversikt (refereegranskat)abstract
- Amplification of innate immune responses by endogenous danger-associated molecular patterns (DAMPs) promotes inflammation. The involvement of S100A8 and S100A9, DAMPs belonging to the S100 calgranulin family, in the pathogenesis of cardiovascular disease is attracting an increasing amount of interest. S100A8 and S100A9 (also termed MRP8 and MRP14) preferentially form the S100A8/A9 heterodimer (MRP8/14 or calprotectin) and are constitutively expressed in myeloid cells. The levels of circulating S100A8/A9 in humans strongly correlate to blood neutrophil counts and are increased by traditional cardiovascular risk factors such as smoking, obesity, hyperglycemia, and dyslipidemia. S100A8/A9 is an endogenous ligand of toll-like receptor 4 (TLR4) and of the receptor for advanced glycation end products (RAGE) and has been shown to promote atherogenesis in mice. In humans, S100A8/A9 correlates with the extent of coronary and carotid atherosclerosis and with a vulnerable plaque phenotype. S100A8/A9 is locally released following myocardial infarction and amplifies the inflammatory responses associated with myocardial ischemia/reperfusion injury. Elevated plasma levels of S100A8/A9 are associated with increased risk of future coronary events in healthy individuals and in myocardial infarction survivors. Thus, S100A8/A9 might represent a useful biomarker and therapeutic target in cardiovascular disease. Importantly, S100A8/A9 blockers have been developed and are approved for clinical testing.
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