There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal ...alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction.
Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood.
Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group.
In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction.
Abstract Objective USPIOs are used clinically as contrast agent for magnetic resonance imaging (MRI) of lymph nodes, and in research settings for MRI of macrophages in atherosclerotic lesions. ...However, T2* weighted (T2*w) imaging can lead to “blooming” with overestimation of the area occupied by USPIOs. In this study, plaque uptake of USPIOs in atherosclerotic mice was investigated in the presence and absence of circulating monocytes. The influence of peri-aortic lymph node uptake on the interpretation of T2*w images of the aortic wall was studied. Methods Atherosclerotic mice were fed an atherogenic diet and were randomized to total body irradiation or non-irradiation. After 2 days, T2*w MRI of the abdominal aorta was performed, followed by intravenous administration of 100 μmol/kg USPIOs ( t = 0). At t = 3 and 5 days MRI of the abdominal aorta was repeated. Animals were sacrificed and histological evidence for iron uptake by aortic wall and lymph nodes was compared with the degree of focal signal loss on in vivo MR images. Results Aortic walls in irradiated and non-irradiated mice, but also in healthy wild-type mice, showed signal loss on T2*w MRI. Signal loss however did not correspond with histological evidence of USPIO uptake by aortic wall but by peri-aortic lymph nodes. Conclusions The versatility of USPIOs as a negative MR contrast agent for both lymph node staging and atherosclerosis may limit the use for detection of atherosclerotic lesions in vessels where lymph nodes are highly prevalent.
Background Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a ...therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. Methods and Findings Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. Conclusions For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a strong predictor for primary stroke.
We presented a novel experimental aneurysm model for studies in left ventricular (LV) reconstruction techniques and assessed LV function. In eight pigs, the LV radius and geometry were enlarged ...surgically on the beating heart by inserting an aortic allograft construct. Haemodynamics and LV dimensions were assessed by echocardiography at baseline and under dobutamine stress. Surgery was successfully performed without lethal blood loss or arrhythmias. LV end-diastolic and end-systolic short-axis areas increased from 13.0 ± 1.7 to 17.0 ± 4.3 cm2 (P = 0.001) and from 4.0 ± 0.9 to 13.0 ± 2.6 cm2 (P = 0.001), respectively. Stroke volume decreased from 56 ± 11 to 33 ± 16 ml (P = 0.001). Incremental dobutamine infusion concurred with a biphasic response on fractional area shortening. Mitral valve insufficiency ranging from grades 2 to 4 was observed. In the pig, a novel, reproducible aneurysm model for acute cardiac dysfunction was created on the beating heart. Innovative (surgical) strategies for (staged) reconfiguration of the ventricle, e.g. adjustable Dor procedures and stepwise volume restraining cardiac support devices, can be tested for efficacy using this acute model.
Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear ...stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown.
PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up.
Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.
Matrix metalloproteinase (MMP) activation is an essential feature of pathological and physiological arterial enlargement or shrinkage. Recently, furin-activated membrane type-1 MMP (MT1-MMP) was ...identified as the in vivo activator of MMP2 in mice. Although arterial enlargement and shrinkage are important in several pathological processes, this proprotein convertase–MT1-MMP axis has not been described during arterial remodeling. In rabbit femoral and carotid arteries, we report an increase in furin and MT1-MMP mRNA levels before and at the onset of arterial remodeling followed by an increase in activated MMP2. This reveals the presence of the proprotein convertase–MT1-MMP axis in flow-induced arterial remodeling and identifies furin as a possible target for local intervention in pathological arterial remodeling.
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