Immunologic Responses in Biological and Mechanical Valve Prostheses: Inflammation and Functionality Are Not Always Related.

BACKGROUND AND AIM OF THE STUDY: The aim of this retrospective study was to evaluate the inflammatory response in patients with aortic and/or mitral prostheses, and to correlate the level of inflammatory markers with prosthesis functionality. METHODS: A total of 48 patients with biological or mechanical prostheses was included in the study, in which levels of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, -4, and -6, interferon-gamma (IFNγ), osteopontin (OPN), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), endothelin-1 and C-reactive protein were analyzed. Functionality of the prosthesis was evaluated using transthoracic echocardiography at three years after surgery. RESULTS: The mean period from the date of surgery was seven years. High levels of IL-1 were found in patients with mechanical prostheses compared to those with bioprostheses (p = 0.04). Patients with aortic bioprostheses and stenosis had higher levels of OPN and endothelin-1, those with aortic mechanical prostheses with stenosis had increased levels of matrix metalloproteinase (MMP)-9, OPN and ICAM, and those with aortic mechanical leakage had increased levels of MMP-1 and endothelin-1. In mitral bioprostheses with leakage of endothelin-1, ICAM and MMP-9 levels were increased, while in mechanical prostheses with leakage there were increases of ICAM and endothelin-1. Tricuspid bioprostheses with double lesions had increased levels of OPN and endothelin-1. CONCLUSIONS: Valvular dysfunction was similar across the types of prosthesis material. IL-1 was increased in subjects with mechanical prostheses independently of dysfunction, while in biological prostheses there were increases in OPN and endothelin-1, and these were related to valvular dysfunction. Given that in the analysis of durability and functionality there were no significant differences between biological and mechanical prostheses, biological prostheses may represent the first treatment option in patients with low economic resources, the elderly, and even young patients.

Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation.

BACKGROUND & AIMS: Butyrate is a four-carbon fatty acid that presents anti-inflammatory, anti-oxidative and apoptotic properties in colon and several cell lines. Because atherosclerosis has important oxidative and inflammatory components, butyrate could reduce oxidation and inflammation, impairing atherogenesis. We evaluated the effects of butyrate supplementation of butyrate on atherosclerosis and its mechanisms of action. METHODS AND RESULTS: ApoE knockout mice were fed on chow diet or 1% butyrate-supplemented chow diet (Butyrate) for 10 weeks to assess atherosclerosis lesions area and inflammatory status. Macrophage and endothelial cells were also pretreated with butyrate (0.5 mM) for 2 h before oxLDL stimulation to study oxLDL uptake and pro and anti-inflammatory cytokine production. Butyrate reduced atherosclerosis in the aorta by 50%. In the aortic valve, butyrate reduced CCL2, VCAM1 and MMP2 productions in the lesion site, resulting in a lower migration of macrophage and increased collagen depositions in the lesion and plaque stability. When EA.hy926 cells were pretreated with butyrate, oxLDL uptake, CD36, VCAM1, CCL2 TNF, IL1ß and IL6 productions were reduced, whereas IL10 production was increased. These effects were accompanied by a lower activation of NFκB due to a lower nuclear translocation of the p65 subunit. CONCLUSION: Oral butyrate is able to slow the progression of atherosclerosis by reducing adhesion and migration of macrophages and increasing plaque stability. These actions are linked to the reduction of CD36 in macrophages and endothelial cells, decreased pro-inflammatory cytokines and lower activation of NFκB all of these data support a possible role for butyrate as an atheroprotective agent.

Evaluation of humoral immune response to donor HLA after implantation of cellularized versus decellularized human heart valve allografts.

We have evaluated the development of antibodies in response to donor allograft valve implant in patients who received cellularized and decellularized allografts and determined possible immunogenic epitopes considered responsible for antibodies reactivity. Serum samples from all recipients who received cellularized allografts or decellularized allografts were collected before valve replacement and at 5, 10, 30 and 90 days post-operatively and frozen until required. Tests were performed using the Luminex-based single human leukocyte antigen (HLA)-A, -B, -C and HLA-DR, -DQ antigen microsphere assay. To determine possible immunogenic epitopes, we used the HLAMatchmaker (HLAMM) software if applicable. Decellularized grafts elicited lower levels of anti-HLA class I and II antibody formation after implantation than cellularized allografts. All patients from cellularized group presented donor-specific antibodies class I and II within 3 months of observation period. In HLAMM analysis, the cellularized group had significantly higher numbers of immunogenic epitopes than decellularized group for both class I and II (p: 0.002 - cl I / p: 0.009 - cl II / p: 0.004 - cl I and II). Our findings demonstrate that the anti-HLA antibodies detected in the cellularized group were against donor HLA possible immunogenic epitopes and that in the decellularized group the anti-HLA antibodies were not against donor HLA possible immunogenic epitopes. These findings lead us to suggest that choosing sodium dodecyl sulfate decellularization process is the best alternative to decrease the immunogenicity of allograft valve transplant.