Novel small leucine-rich repeat protein podocan is a negative regulator of migration and proliferation of smooth muscle cells, modulates neointima formation, and is expressed in human atheroma.

Background: Smooth muscle cell (SMC) migration and proliferation critically influence the clinical course of vascular disease. We tested the effect of the novel small leucine-rich repeat protein podocan on SMC migration and proliferation using a podocan-deficient mouse in combination with a model of arterial injury and aortic explant SMC culture. In addition, we examined the effect of overexpression of the human form of podocan on human SMCs and tested for podocan expression in human atherosclerosis.

The imbalance between proliferation and apoptosis contributes to degeneration of aortic valves and bioprostheses.

Background: The pathomechanisms underlying aortic valve degeneration are incompletely understood. Therefore, the aim of our work was to assess the quantitative changes of proliferation and apoptosis accompanied by cellular phenotype alternations and matrix secretionin aortic sclerotic and stenotic valves and degenerative bioprostheses, as well as to detect the expression pattern of the rapamycin receptor FKBP12 across these three valve types.

Methods: Mild-to-moderate sclerotic and stenotic valves and degenerative bioprostheses from 30 patients (n = 10 per group) were collected at autopsy or by surgery.

Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation.

Objective: Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease.

Prevalence of intimal heat shock protein 60 homologues in unstable angina and correlation with anti-heat shock protein antibody titers.

Heat shock proteins (HSPs) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Human (h) HSP60 is upregulated under stress conditions and serves as a target for cross-reactive cytotoxic HSP-serum-antibodies. The present study evaluates the expressions of hHSP60 and its homologue chlamydial (c) HSP60 in advanced human coronary lesions and correlates intimal tissue-bound HSP expressions with circulating HSP-antibodies.

Degenerative valve disease and bioprostheses: risk assessment, predictive diagnosis, personalised treatments.

Aortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic.

The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro.

The complement component C5a is formed during activation of the complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased.

Antiplatelet effects of antidepressant treatment: a randomized comparison between escitalopram and nortriptyline.

Introduction: Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation.

Methods: Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting.

Impact of intimal pathogen burden in acute coronary syndromes--correlation with inflammation, thrombosis, and autoimmunity.

Background: Increasing evidence supports a link between serological evidence of pathogen burden (PB) and the risk for future cardiovascular events. Our study evaluates the intimal presence of 4 pathogens in atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect on the expression of intimal C-reactive protein (CRP), tissue factor (TF) and human heat-shock protein 60 (hHSP60).

Methods: Coronary atherectomy specimens retrieved from 60 primary lesions of patients with ACS (n=35) or SA (n=25) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (Cpn), Helicobacter pylori (HP), Cytomegalovirus (CMV) and Epstein–Barr Virus (EBV) and for the expression of CRP, TF, and hHSP60.

Pathogen burden in degenerative aortic valves is associated with inflammatory and immune reactions.

Background And Aim Of The Study: The presence of five pathogens was assessed, together with a possible correlation of the total pathogen burden on inflammation and (auto)immunity in aortic stenosis (AS) and degenerative aortic valve bioprosthesis (BP).

Methods: Diseased valve specimens from a total of 68 patients (52 with AS, 16 with BP) were studied. The presence and localization was assessed of Chlamydia pneumoniae (cHSP60), Helicobacter pylori (HP), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV), as well as of macrophages (CD68), C-reactive protein (CRP) and human heat shock protein 60 (hHSP60), by using immunohistochemical and morphometric analyses.

Apoptosis-regulated survival of primarily extravascular cells in proliferative active poststent neointima.

Background: Increased proliferation, mitigated apoptosis, and recruitment of primarily extravascular cells to injured vessels are important processes during neointima formation. Therefore, the goal of this study was to assess the spatiotemporal balance between proliferation and apoptosis and the influence of apoptosis on the survival of primarily extravascular cells in in-stent neointima.

Methods: Minipigs underwent stent implantation to abdominal aortic segments.

Prediction of degeneration of native and bioprosthetic aortic valves: issue-related particularities of diabetes mellitus.

Degenerative aortic valve stenosis is the leading cause of heart valve disease in elderly resulting in significant morbidity and mortality. Although aortic stenosis has been recognized as a complex inflammatory and well-regulated process, its exact pathomechanisms are still largely unknown. Assessment by Echocardiography, Electron Beam Computed Tomography and Multislice Computed Tomography is useful for monitoring of disease progression.

Differential profile of the OPG/RANKL/RANK-system in degenerative aortic native and bioprosthetic valves.

Background And Aim Of The Study: Although degenerative calcific aortic valve stenosis is the most common valvular disease among the elderly, neither the etiology underlying the condition nor degeneration of the bioprostheses is yet fully understood. The study aim was to assess the expression profile of those OPG/RANKL/RANK-system determinants known to act as key regulators of bone metabolism and the immune system in calcific aortic valve stenosis and porcine aortic bioprostheses.

Methods: Valve probes from a total of 69 patients (41 with end-stage aortic stenosis, 11 with mild-to-moderate aortic sclerosis, 17 with degenerative porcine aortic bioprostheses) were explanted either during surgery or at autopsy.

Increased expression of C-reactive protein and tissue factor in acute coronary syndrome lesions: Correlation with serum C-reactive protein, angioscopic findings, and modification by statins.

Background: Serum C-reactive protein (CRP) is a strong risk predictor of cardiovascular events, and tissue factor (TF) plays a central role in thrombus formation of advanced atherosclerotic plaques. Aim of the present study was to quantify in situ CRP and TF in coronary atherectomy specimens associated with acute coronary syndromes (ACS) or stable angina (SA). In addition, the effect of statin treatment on both intimal determinants was analyzed.

Cells of primarily extravascular origin in neointima formation following stent implantation: coordinated expression of endothelial progenitor, dendritic and neural crest-derived cells.

Objectives: In-stent restenosis due to neointima formation is a major limitation following stent implantation. Recently, several studies reported mobilization of primarily extravascular cells to the arterial sites after balloon angioplasty. Therefore, the goal of the present study was to assess the coordinated neointimal expression of endothelial progenitor, dendritic and neural crest-derived cells after stent implantation.

Neointimal expression of rapamycin receptor FK506-binding protein FKBP12: postinjury animal and human in-stent restenosis tissue characteristics.

Despite excellent clinical results for sirolimus (rapamycin)-eluting stents, the exact mechanisms of antirestenotic activity and affected cellular targets are incompletely understood. Therefore, we determined the presence and tem- porospatial expression pattern of FKBP12, the primary intracellular receptor of rapamycin, in rat carotid arteries after balloon injury, as well as in human in-stent restenosis and primary stable coronary atheroma. FKBP12 expression was assessed by immunohistochemistry.

Sequential patterns of chemokine- and chemokine receptor-synthesis following vessel wall injury in porcine coronary arteries.

Inflammation plays a central role in vascular repair, and spreads into perivascular tissue (PVT) following angioplasty. Chemokines (CK) and chemokine receptors (CKR) are key determinants of inflammatory chemotaxis. We sought to assess the arterial and perivascular expression of the CK CCL2 and CXCL2, and the CKR CCR2, CCR5, and CXCR4 in balloon-injured porcine coronary arteries.

Is the degeneration of aortic valve bioprostheses similar to that of native aortic valves? Insights into valvular pathology.

Aortic stenosis (AS) is the most common valvular disease requiring valve replacement with a prevalence of 2-4% in adults greater than or equal to 65 years of age. There is increasing evidence that AS is an active inflammatory process that is highly regulated, displaying multiple hallmarks of atherosclerosis. Clinically, the definite therapy of advanced AS is prosthetic valve replacement.

Differential antiplatelet effects of angiotensin converting enzyme inhibitors: comparison of ex vivo platelet aggregation in cardiovascular patients with ramipril, captopril and enalapril.

Background: Increasing evidence suggests that angiotensin converting enzyme (ACE) inhibitors exert antithrombotic effects. Based on the assumption of differential effects of various ACE inhibitors on coagulation, the aim of the present study was to evaluate the coagulative activities of cardiovascular (CV) patients treated with either ramipril, captopril, and enalapril, and to compare these with patients treated with established antithrombotics such as aspirin (ASA) and clopidogrel or none of these medication.

Methods: Blood samples of 320 CV patients with coronary artery disease and/or arterial hypertension were analyzed by wholeblood aggregometry.

Non-invasive imaging of a coronary bypass stenosis using CT angiography in a patient with negative stress testing.

In patients with a low or intermediate probability of a coronary artery disease, ultrafast computer tomography (CT) of the coronary arteries and bypass grafts offer a novel approach for the evaluation of the coronary anatomy. The presented case impressively demonstrated the capability of ultrafast CT to show precisely the extent and localisation of a bypass artery stenosis in a patient with mild chest discomfort but negative stress testing. However, widespread screening of coronary artery disease with non-invasive imaging modalities can not be recommended until validated in larger studies that a complete visualization of all coronary arteries and bypass grafts can be achieved.

Cells of primarily extra-valvular origin in degenerative aortic valves and bioprostheses.

Aims: We assessed aortic valves from patients with non-rheumatic aortic valve stenosis (AS) and with degenerative aortic valve bioprostheses (BP) for the presence of progenitor cell and leukocyte subtype-specific markers.

Methods And Results: Diseased valve probes from a total of 87 patients (60 AS and 27 BP) were studied. We assessed presence and localization of endothelial progenitor cells (EPCs: CD34, CD133), dendritic cells (DCs: S100), T-lymphocytes (CD3), and macrophages (CD68) by immunohistochemical and morphometric analyses.