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2 results on '"Sagan, Agnieszka"'

1. Mechanisms of oxidative stress in human aortic aneurysms — Association with clinical risk factors for atherosclerosis and disease severity

Author

Guzik, Bartłomiej, Sagan, Agnieszka, Ludew, Dominik, Mrowiecki, Wojciech, Chwała, Maciej, Bujak-Giżycka, Beata, Filip, Grzegorz, Grudzień, Grzegorz, Kapelak, Bogusław, Żmudka, Krzysztof, Mrowiecki, Tomasz, Sadowski, Jerzy, Korbut, Ryszard, and Guzik, Tomasz

Subjects
Male, Pathology, Nitric Oxide Synthase Type II, 030204 cardiovascular system & hematology, medicine.disease_cause, Severity of Illness Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Superoxides, Medicine, chemistry.chemical_classification, 0303 health sciences, NADPH oxidase, biology, Superoxide, NOX4, Middle Aged, 3. Good health, NAD(P)H oxidase, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, macromolecular substances, Article, 03 medical and health sciences, Internal medicine, Humans, cardiovascular diseases, Xanthine oxidase, Aged, 030304 developmental biology, Inflammation, Reactive oxygen species, business.industry, Aortic abdominal aneurysm, NADPH Oxidases, Atherosclerosis, Oxidative Stress, Endocrinology, chemistry, biology.protein, P22phox, Oxidant stress, business, Oxidative stress, Aortic Aneurysm, Abdominal
Abstract

Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2radical dot−) production in human AAA.\ud Methods and results:\ud \ud AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n = 16) than in risk factor matched controls (n = 16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2radical dot− in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size.\ud Conclusions:\ud \ud Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients.

Published
2013

2. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension.

Author

Mikolajczyk, Tomasz P., Nosalski, Ryszard, Szczepaniak, Piotr, Budzyn, Klaudia, Osmenda, Grzegorz, Skiba, Dominik, Sagan, Agnieszka, Jing Wu, Vinh, Antony, Marvar, Paul J., Guzik, Bartlomiej, Podolec, Jakub, Drummond, Grant, Lob, Heinrich E., Harrison, David G., and Guzik, Tomasz J.

Subjects
THERAPEUTICS, HYPERTENSION, IMMUNOLOGY of inflammation, CHEMOKINE receptors, T cell receptors, TREATMENT of vascular diseases, ADIPOSE tissues
Abstract

Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs.3.5 ± 1.1;P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES−/− knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang IIvs.15 ± 4% in RANTES−/−), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8+ and double-negative CD3+CD4−CD8− T cells in perivascular space and reduced vascular oxidative stress while FoxP3+ T-regulatory cells were unaltered. IFN-γex vivocaused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R= −0.3,P< 0.01) or endothelial injury marker von Willebrand factor (R= +0.3;P< 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation. [ABSTRACT FROM AUTHOR]

Published
2016
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