Deletion/Deletion Genotype of Angiotensin-I Converting Enzyme Gene is not Associated with Coronary Artery Disease in Caucasians with Type 2 Diabetes

In this study we analyzed the contribution of genetic variability of the insertion/deletion (I/D) polymorphism of the angiotensin-I converting enzyme (ACE) gene to the predisposition for coronary artery disease (CAD) in a group of patients with type 2 diabetes. The I/D ACE gene polymorphism was tested in 366 Caucasians with type 2 diabetes: 148 cases with CAD and 218 subjects with no history of CAD. We failed to demonstrate that the ACE DD genotype was a risk factor for CAD in Caucasians with type 2 diabetes (OR 2.0, 95 % CI 0.9–4.7; p=0.1). In conclusion, we provide evidence that the ACE deletion/deletion genotype is not a risk factor for CAD in Caucasians with type 2 diabetes

Deficiency of mast cells in coronary artery endarterectomy of male patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes is an important risk factor for the development of coronary artery disease (CAD). Focal or diffuse inflammation is often present in the vessels of patients with CAD. Mast cells are frequently present in the plaques as well as in the inflammatory infiltrates in the atherosclerotic vessel wall. In the study we wanted to examine whether there are differences in the morphology, number and distribution of mast cells and in their ability to modify the atherosclerotic process in coronary arteries (CA) in the diabetic <it>vs</it>. the hypertensive population of patients with CAD.</p> <p>Methods</p> <p>Coronary artery endarterectomy specimens were obtained from patients with diabetes or hypertension as the only risk factor for CAD. The specimens were stained with haematoxylin-eosin and Sulphated Alcian Blue for mast cells and with immunofluorescent methods for fibrinogen-fibrin and IgG deposits in the vessel wall. Both morphological and stereological assessments were conducted for mast cells and mononuclear cell infiltrates.</p> <p>Results</p> <p>The histological analysis of the vessel wall of diabetic patients in comparison with hypertensive patients showed a damaged endothelial cells layer and deposits of fibrin-fibrinogen and IgG in the tunica intima and media. The stereological count revealed a diminished numerical density of mast cells and a significantly higher volume density of the mononuclear cells. Mast cells displayed cytoplasmic vacuolization, extracellular extrusion of granule and pyknotic nuclei.</p> <p>Conclusion</p> <p>This preliminary study suggests that the impaired mast cells might be the reason for more extensive inflammatory and immunologic atherosclerotic changes in the CA vessel wall of CAD patients with type 2 diabetes.</p> <p>Trial registration</p> <p>134/88;C3-0564-381-92</p

Skin and kidney histological changes in graft-versus-host disease (GVHD) after kidney transplantation.

Kidney transplantation (Ktx) is generally performed during end stage renal disease due to a loss of the kidneys' ability to filter wastes from the circulatory system. Acute graft-versus-host disease (GVHD) after Ktx is a life-threatening complication that progresses to organ failure, systemic complications, and death. The current study evaluated the significance of histologic findings of GVHD as obtained from skin biopsies following Ktx in swine. A swine model of Ktx with tacrolimus-based immunosuppression was used to assess possible correlations between acute-graft-cellular rejection and skin histological findings for prediction of GVHD. Animals were divided into a Ktx treatment group or a control group with no Ktx and skin and kidney biopsies were histologically assessed at postoperative days 0, 15, 30, 45 and 60. Skin samples were analyzed and classified from grade 1 to 4 of skin GVHD and the major histopathological changes of kidney acute cellular rejection were described using Banff's score system. We observed a significant linear correlation between the histological grading values of skin biopsy changes and the histological grading values of kidney biopsies (Kendall's tau_b=0.993) in the Ktx experimental group. No histological changes were observed in controls. Our findings demonstrate the diagnostic value of staging skin GVHD after Ktx and suggest it's future utility for monitoring long term Ktx-induced changes. (C) 2011 Association of Basic Medical Sciences of FBIH. All rights reserve

Skin and kidney histological changes in graft-versus-host disease (GVHD) after kidney transplantation

Kidney transplantation (Ktx) is generally performed during end stage renal disease due to a loss of the kidneys’ ability to filter wastes from the circulatory system. Acute graft-versus-host disease (GVHD) after Ktx is a life-threatening complication that progresses to organ failure, systemic complications, and death. The current study evaluated the significance of histologic findings of GVHD as obtained from skin biopsies following Ktx in swine. A swine model of Ktx with tacrolimus-based immunosuppression was used to assess possible correlations between acute-graft-cellular rejection and skin histological findings for prediction of GVHD. Animals were divided into a Ktx treatment group or a control group with no Ktx and skin and kidney biopsies were histologically assessed at postoperative days 0, 15, 30, 45 and 60. Skin samples were analyzed and classified from grade 1 to 4 of skin GVHD and the major histopathological changes of kidney acute cellular rejection were described using Banff’s score system. We observed a significant linear correlation between the histological grading values of skin biopsy changes and the histological grading values of kidney biopsies (Kendall’s tau_b=0.993) in the Ktx experimental group. No histological changes were observed in controls. Our findings demonstrate the diagnostic value of staging skin GVHD after Ktx and suggest it’s future utility for monitoring long term Ktx-induced changes

Immune cells and vasa vasorum in the tunica media of atherosclerotic coronary arteries

In coronary artery disease (CAD), the disruption of the tunica media immune privilege manifests as increased leukocyte infiltration and the formation of vasa vasorum. We aimed to characterize the immune privilege status of the tunica media in human coronary arteries (CAs) with atherosclerotic plaques, by comparing the abundance and composition of immune-cell infiltrates within the individual arterial-wall layers, and by evaluating vasa vasorum neovascularization of the tunica media. The tissue samples were obtained from 36 symptomatic patients with diffuse CAD (aged 60–72 years) who underwent coronary endarterectomy. T and B cells, macrophages and endothelial cells in the CAs were detected by immunohistochemistry. Morphological analysis of CAs showed significant atherosclerotic changes in all specimens. In the media, we observed damage and loss of smooth muscle cells, destruction of the extracellular matrix architecture, and fibrosis. There were 43.3% of immune cells in the intima, 50% in the adventitia, and 6.7% in the media. In the media, 51.1% of the immune cells were T cells (p ˂ 0.001 compared to B cells and macrophages; ANOVA, Scheffe post hoc analysis), 23.5% were B cells, and 25.4% were macrophages. The number of vasa vasorum in the media was 1 in 38.9% of CAs, 2–3 in 36.1%, and ≥4 in 25% of CAs. Our results indicate that, in atherosclerotic CAs, the immune privilege of the media is disrupted by the infiltration of T and B cells, macrophages, and the presence of vasa vasorum

Polymorphisms of the PPAR-γ (rs1801282) and Its Coactivator (rs8192673) Have a Minor Effect on Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

Background. The present study was designed to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with markers of carotid and coronary atherosclerosis in Caucasians with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled in the cross-sectional study. Markers of carotid atherosclerosis were assessed ultrasonographically. In 215 out of 595 subjects with T2DM, a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of either rs1801282 or rs8192673 was performed using KASPar assays. Results. In our study, we demonstrated an effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM in univariate and in multivariable linear regression analyses. Finally, we did not demonstrate any association between either rs1801282 or rs8192673 and markers of coronary atherosclerosis. Conclusions. In our study, we demonstrated a minor effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM. Moreover, we demonstrated a minor effect of the rs8192673 on CIMT progression in the 3.8-year follow-up in Caucasians with T2DM

Impact of Cusp-Overlap View for TAVR with Self-Expandable Valves on 30-Day Conduction Disturbances

Background and Aim. Conduction disturbances leading to permanent pacemaker implantation (PPMI) remains a common complication for TAVR procedures, particularly when self-expanding valves are used. We compared the 30-day incidence of new-onset left bundle branch block (LBBB) and permanent pacemaker implantation (PPMI) rate between two consecutive groups using either conventional 3-cusp coplanar view (CON) and right/left cusp-overlap view (COVL) for implantation. Methods and Results. We retrospectively compared 257 consecutive patients undergoing TAVR with self-expandable valves using either CON (n = 101) or COVL (n = 156) in four intermediate/low volume centers. There were no significant differences in baseline characteristics between the groups. The 30-day incidence of new-onset LBBB (12.9% vs. 5.8%; p=0.05) and PPMI rate (17.8% vs. 6.4%; p=0.004) was significantly lower when using the COVL implantation view. There was no difference between the CON and COVL groups in 30-day incidence of death (4.9% vs. 2.6%), any stroke (0% vs. 0.6%), and the need for surgical aortic valve replacement (0% for both groups). Conclusion. Using the COVL view for implantation, we achieved a significant reduction of the LBBB and PPMI rate after TAVR in comparison with the traditional CON view, without compromising the TAVR outcomes when using self-expandable prostheses