Abdominal Aortic Aneurysm (AAA) is a major cause of cardiovascular mortality. Adverse changes in vascular phenotype act in concert with chronic inflammation to promote AAA progression. Perivascular adipose tissue (PVAT) helps maintain vascular homeostasis but when inflamed and dysfunctional, can also promote vascular pathology. Previous studies suggested that PVAT may be an important site of vascular inflammation in AAA; however, a detailed assessment of leukocyte populations in human AAA, their anatomic location in the vessel wall and correlation to AAA size remain undefined. Accordingly, we performed in depth immunophenotyping of cells infiltrating the pathologically altered perivascular tissue (PVT) and vessel wall in AAA samples at the site of maximal dilatation (n = 51 patients). Flow cytometry revealed that T cells, rather than macrophages, are the major leukocyte subset in AAA and that their greatest accumulations occur in PVT. Both CD4+ and CD8+ T cell populations are highly activated in both compartments, with CD4+ T cells displaying the highest activation status within the AAA wall. Finally, we observed a positive relationship between T cell infiltration in PVT and AAA wall. Interestingly, only PVT T cell infiltration was strongly related to tertiles of AAA size. In summary, this study highlights an important role for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA.
Endothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14CD16 "classical - Mon1", CD14CD16 "intermediate - Mon2" and CD14CD16 "nonclassical - Mon3"), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium-nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14CD16 "nonclassical" and low CD14CD16 "classical" monocytes presented impaired endothelial function. High frequency of CD14CD16 "nonclassical" monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14CD16 monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β=0.18 p=0.04 and β=-0.19 p=0.03, respectively). In summary, our data indicate that CD14CD16 "nonclassical" monocytes are associated with more advanced vascular dysfunction measured as NO- bioavailability and vascular reactive oxygen species production.
A b s t r a c tIntroduction: There are no reliable data regarding the prevalence of rheumatoid arthritis (RA) in Poland. Material and methods: The first stage was a face-to-face survey on a nationwide representative sample of 3000 people, which identified respondents with a physician-confirmed diagnosis of RA. The second stage was a survey of RA patients, which characterized the disease course and treatment. It was evaluated by analysis of a representative group of 1957 RA patients in routine clinical practice. Results: The overall RA prevalence in Poland was 0.9% (95% CI: 0.6-1.2%), 1.06% for women, 0.74% for men. 78% were female, mean age was 56 and mean disease duration 7 years. Younger patients (< 50) remained professionally active in 90% of cases. 30% of patients were diagnosed within 3 months of the first RA symptoms, while for 17% it took more than 1 year. 56% of newly diagnosed patients were characterized by high disease activity (DAS-28 > 5.1). Presently, low disease activity (DAS-28<3.2) was found in 38,5% of patients. In Poland, 94% of patients have been treated with non-steroid anti-inflammatory drugs, almost 80% with glucocorticoids. Meanwhile, methotrexate, as an anchor drug in Poland, has been used by 80% of patients, biological agents by 2.94% of patients. Conclusions: This is the first cross-sectional population-based epidemiological study regarding prevalence of RA in the adult Polish population. The results demonstrate a high prevalence, falling within the upper boundary estimates for Europe. Despite ongoing treatment, the majority still have moderate to high disease activity, and the use of biological therapies is low.
SummaryIntraluminal thrombus formation in aortic abdominal aneurysms (AAA) is associated with adverse clinical prognosis. Interplay between coagulation and inflammation, characterised by leukocyte infiltration and cytokine production, has been implicated in AAA thrombus formation. We studied leukocyte (CD45+) content by flow cytometry in AAA thrombi from 27 patients undergoing surgical repair. Luminal parts of thrombi were leukocyte-rich, while abluminal segments showed low leukocyte content. CD66b+ granulocytes were the most prevalent, but their content was similar to blood. Monocytes (CD14+) and T cells (CD3+) were also abundant, while content of B lymphocytes (CD19+) and NK cells (CD56+CD16+) were low. Thrombi showed comparable content of CD14highCD16-monocytes and lower CD14highCD16+ and CD14dimCD16+, than blood. Monocytes were activated with high CD11b, CD11c and HLA-DR expression. Total T cell content was decreased in AAA thrombus compared to peripheral blood but CD8 and Correspondence to: Prof. Tomasz J Guzik, MD, PhD Department of Internal and Agricultural Medicine Jagiellonian University School of Medicine J Dietl Hospital, Ul. Skarbowa 1 31-121 Cracow, Poland E-mail: tguzik@cm-uj.krakow.pl CD3+CD4-CD8-(double negative T cell) contents were increased in thrombi. CD4+ cells were lower but highly activated (high CD69, CD25 and HLA-DR). No differences in T regulatory (CD4+CD25+FoxP3+) cell or pro-atherogenic CD4+CD28null lymphocyte content were observed between thrombi and blood. Thrombus T cells expressed high levels of CCR5 receptor for chemokine RANTES, commonly released from activated platelets. Leukocyte or T cell content in thrombi was not correlated with aneurysm size. However, CD3+ content was significantly associated with smoking in multivariate analysis taking into account major risk factors for atherosclerosis. In conclusion, intraluminal AAA thrombi are highly inflamed, predominantly with granulocytes, CD14highCD16-monocytes and activated T lymphocytes. Smoking is associated with T cell infiltration in AAA intraluminal thrombi.
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