Inflammatory aortic abdominal aneurysm - immunophenotypic characterization of inflammatory infiltrate

No abstract available

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

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. Methods and results: 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. Conclusions: 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

Przezskórna angioplastyka Y-pomostu żylnego u pacjenta z niestabilną dławicą piersiową : czy zwężenie bifurkacji Y-pomostu żylnego jest nadal wyzwaniem?

Pacjenta w wieku 71 lat po przebytej operacji pomostowania aortalno-wieńcowego przyjęto do Kliniki Kardiologii Interwencyjnej Krakowskiego Szpitala Specjalistycznego im. Jana Pawła II z powodu ostrego zespołu wieńcowego - niestabilnej dławicy piersiowej. W angiografii wieńcowej wykazano obecność istotnego zwężenia rozwidlonego żylnego pomostu wieńcowego jako ostatniego funkcjonującego naczynia. Po kwalifikacji przez lokalny zespół sercowy u pacjenta wykonano angioplastykę rozwidlonego pomostu żylnego z implantacją samorozprężalnego stentu uwalniającego sirolimus (Stentys). W opisie przypadku jest mowa o technicznych aspektach, takich jak wykorzystanie urządzeń do wspomagania funkcji lewej komory, dodatkowych metod obrazowania wieńcowego, rodzaju dostępu zabiegowego, rodzaju stentu i dystalnej protekcji naczynia. Pacjent z licznymi obciążeniami i istotnie obniżoną frakcją wyrzutową lewej komory jest raczej kandydatem do przezskórnej rewaskularyzacji niż do klasycznej operacji. Osiem miesięcy po zabiegu pacjentowi implantowano automatyczny kardiowerter-defibrylator w ramach prewencji pierwotnej nagłej śmierci sercowej w związku z objawową przewlekłą niewydolnością serca. W dyskusji omówiono problem długoterminowego efektu leczenia przezskórnego w tej grupie chorych. Rewaskularyzacja wieńcowa pacjenta z silnymi objawami ze zwężeniem ostatniego funkcjonującego naczynia wieńcowego powinna być obowiązkowa, choć liczne choroby współtowarzyszące zwiększają ryzyko zarówno operacji klasycznej, jak i przezskórnej angioplastyki. Zasadnicze pytanie brzmi: leczyć zabiegowo czy zachowawczo?A 71 year-old patient with a history of coronary artery bypass grafting was admitted to the Department of Interventional Cardiology, John Paul II Hospital, Krakow with acute coronary syndrome - unstable angina. Coronary angiography revealed significant narrowing of a bifurcated venous bypass graft as the last remaining vessel. After consultation from the Heart Team, he underwent percutaneous coronary angioplasty of the venous bypass with implantation of a selfapposing sirolimus-eluting stent (Stentys). The technical aspects of this procedure, such as the use of a left ventricle assist device, additional imaging (intravascular ultrasound), the type of approach and stent, and the protection of the vessel are discussed in this article. A patient with numerous co-morbidities and severely decreased function of the left ventricle was in fact a candidate for percutaneous revascularisation. Eight months later, the patient had a cardioverter- -defibrillator implanted in primary prevention of sudden cardiac death due to symptomatic chronic heart failure with reduced ejection fraction. This discussion raises the topic of the long-term effectiveness of angioplasty in this group of patients. Myocardial revascularisation in a patient with severe symptoms and a diseased last remaining vessel should be obligatory. However, multiple comorbidities increase the risk of cardiac surgery as well as of percutaneous angioplasty. The critical question here is: should the treatment be invasive or would the better option be optimal medical treatment

Przezskórna angioplastyka Y-pomostu żylnego u pacjenta z niestabilną dławicą piersiową. Czy zwężenie bifurkacji Y-pomostu żylnego jest nadal wyzwaniem?

71 years-old patient with history of CABG was admitted to Department of Interventional Cardiology, John Paul II Hospital, Cracow with acute coronary syndrome – unstable angina. The coronary angiography revealed significant narrowing of bifurcated venous bypass graft as the last remaining vessel. After qualification by the Heart Team he underwent percutaneous coronary angioplasty of venous bypass with implantation of self-apposing sirolimus-eluting stent (Stentys). Technical aspects of procedure such as usage of left ventricle assist device, additional imaging (IVUS), type of approach, stent and protection of vessel were considered in this manuscript. Patient with numerous co-morbidities and severely decreased function of left ventricle was rather candidate for percutaneous revascularization. 8 months later patient had implanted implantable cardioverter-defibrillator in primary prevention of sudden cardiac death due to symptomatic chronic heart failure with reduced ejection fraction. Discussion raises the topic of long-term effectiveness of angioplasty in these group of patients. Myocardial revascularization in patient with severe symptoms and diseased last remaining vessel should be obligatory, however multiple comorbidities increases the risk of cardiac surgery as well as percutaneous angioplasty. Critical question is: to treat invasively or with optimal medical treatment?Pacjenta w wieku 71 lat po przebytej operacji pomostowania aortalno-wieńcowego przyjęto do Kliniki Kardiologii Interwencyjnej Krakowskiego Szpitala Specjalistycznego im. Jana Pawła II z powodu ostrego zespołu wieńcowego — niestabilnej dławicy piersiowej. W angiografii wieńcowej wykazano obecność istotnego zwężenia rozwidlonego żylnego pomostu wieńcowego jako ostatniego funkcjonującego naczynia. Po kwalifikacji przez lokalny zespół sercowy u pacjenta wykonano angioplastykę rozwidlonego pomostu żylnego z implantacją samorozprężalnego stentu uwalniającego sirolimus (Stentys). W opisie przypadku jest mowa o technicznych aspektach, takich jak wykorzystanie urządzeń do wspomagania funkcji lewej komory, dodatkowych metod obrazowania wieńcowego, rodzaju dostępu zabiegowego, rodzaju stentu i dystalnej protekcji naczynia. Pacjent z licznymi obciążeniami i istotnie obniżoną frakcją wyrzutową lewej komory jest raczej kandydatem do przezskórnej rewaskularyzacji niż do klasycznej operacji. Osiem miesięcy po zabiegu pacjentowi implantowano automatyczny kardiowerter-defibrylator w ramach prewencji pierwotnej nagłej śmierci sercowej w związku z objawową przewlekłą niewydolnością serca. W dyskusji omówiono problem długoterminowego efektu leczenia przezskórnego w tej grupie chorych. Rewaskularyzacja wieńcowa pacjenta z silnymi objawami ze zwężeniem ostatniego funkcjonującego naczynia wieńcowego powinna być obowiązkowa, choć liczne choroby współtowarzyszące zwiększają ryzyko zarówno operacji klasycznej, jak i przezskórnej angioplastyki. Zasadnicze pytanie brzmi: leczyć zabiegowo czy zachowawczo

Asymmetric dimethylarginine as a useful risk marker of radial artery calcification in patients with advanced kidney disease

Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor $1\alpha$ ($SDF1\alpha$), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and $SDF1\alpha$ levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between $SDF1\alpha$ and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. Circulating ADMA levels indicate medial arterial calcification in patients with CKD

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as predictors of coronary microcirculatory disease occurrence and outcome in patients with chronic coronary syndrome and no significant coronary artery stenosis

Introduction: Index of microcirculatory resistance assessment is an invasive method of measuring coronary microcirculation function. Association between impaired microcirculatory function and higher rate of cardiovascular events was proven. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio seem to be a promising parameters to predict coronary microcirculatory disease in patients with chronic coronary syndrome. The aim: To determine neutrophil-lymphocyte ratio and platelet-lymphocyte ratio levels in patients with coronary microcirculatory disease and potential association with clinical outcome. Material and methods: 82 consecutive patients with mean age of 67 years, 67% male, were tested for presence of coronary microcirculatory disease using index of microcirculatory resistance. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated based on admission full blood count. Follow-up with major adverse cardiac and cardiovascular events registration was performed (median 24 months). Results: The study showed significantly higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with coronary microcirculatory disease compared to control group (3.58±2.61 vs 2.54±1.09 and 164±87.9 vs 124±36.6 respectively). Higher level of platelet-lymphocyte ratio in patients with coronary microcirculatory disease results in worse MACCE-free survival. Optimal cut-off values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to detect coronary microcirculatory disease were 3.2 and 181.3, respectively. Conclusions: Higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with increased index of microcirculatory resistance value. Platelet-lymphocyte ratio may be used as a predictor of worse outcome in patients with coronary microcirculatory disease

Percutaneous management of long and diffused coronary lesions using newer generation drug-eluting stents in routine clinical practice : long-term outcomes and complication predictors

Long and diffuse coronary lesions (LDCLs) are routinely subjected to percutaneous management, but long‑term clinical outcomes and complication predictors with the use of contemporary stents and techniques remain undetermined. Long and diffuse coronary lesion was defined as a lesion requiring an implantation of 30 mm or longer total stent(s) length (TSL) into one coronary artery (bailouts excluded). There were 290 LDCL interventions with the use of newer generation drug‑eluting stents (DESs cobalt chromium everolimus- or zotarolimus-eluting stents) performed between January 2013 and January 2016. The mean (SD) TSL was 55.5 (16.8) mm. The use of intravascular ultrasound / optical coherence tomography was 17.1%, rotablation, 6.9%, and noncompliant balloon, 88.9%. The median (range) follow‑up duration was 831 (390-1373) days. All‑cause mortality and cardiac death rates were 11.7% and 6.9%, respectively. The myocardial infarction (MI) rate was 6.6%, including target‑vessel MI in 4.1%. The rate of clinically‑driven repeat revascularization was 13.8%, and of definite or probable LDCL stent thrombosis, 7.2%. Overall patient‑oriented adverse event rate (any death, MI, or repeat revascularization) was 25.5%, and device‑oriented rate (cardiac death, target vessel‑MI, or target lesion restenosis), 13.4%. Adverse outcome predictors were chronic kidney disease, acute coronary syndrome as an indication for the procedure, chronic heart failure with reduced left ventricular ejection fraction, multivessel disease, and coexisting peripheral artery disease, but not lesion‑related factors, such as bifurcation, calcification, chronic total occlusion, or TSL. Adverse outcomes following contemporary LDCL management using newer generation DESs in routine clinical practice are associated with clinical patient characteristics rather than lesion characteristics or TSL. We identified high‑risk patient cohorts that may benefit from enhanced surveillance

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

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 II vs. 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-γ ex vivo caused 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.—Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension