Melatonin inhibits macrophage infiltration and promotes plaque stabilization by upregulating anti-inflammatory HGF/c-Met system in the atherosclerotic rabbit: USPIO-enhanced MRI assessment.

Macrophage plays critical roles in the pathogenesis of atherosclerosis (AS), and is an attractive target for detecting and treating vulnerable plaque. Our previous study showed that melatonin (MLT) ameliorated AS by suppressing the pro-inflammatory Toll-like receptor 4/nuclear factor kappa B system in high-fat-fed rabbit. However, it is unknown whether the anti-atherosclerotic properties of MLT are associated with the upregulation of anti-inflammatory hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-Met) system. In present study, we examined whether MLT could inhibit macrophage infiltration and promote plaque stabilization by upregulating HGF/c-Met system with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) assessment in AS rabbit. Rabbits in this study were randomly divided into three groups and treated with a standard diet, high-fat diet, and high-fat diet plus 10 mg/kg/day MLT for 12 weeks, respectively. MLT treatment significantly reversed spotty signal void in 3D-TOF MRI, standard signal intensity reduction in T2WI MRI and aortic luminal area reduction in 2D-TOF MRI of the atherosclerotic abdominal aorta 72 h after USPIO injection. It also decreased serum interleukin-6 (IL-6), intima/media thickness ratio of the abdominal aorta, CD68 and iron-positive areas in the aortic intima, and increased serum IL-10, HGF and c-Met protein expression and the accumulation of vascular smooth muscle cell and collagen fiber in the aortic intima of AS rabbit. Our data demonstrated that MLT significantly decreased plaque macrophage infiltration and promoted plaque stability in AS rabbit assessed by USPIO-enhanced MRI. Remarkably, it was very first revealed that upregulation of anti-inflammatory HGF/c-Met system might contribute to the atheroprotective mechanisms of MLT.

Associations of cardiovascular disease risk factors with abdominal aortic calcium volume and density: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Abdominal aortic calcium (AAC) predicts future cardiovascular disease (CVD) events and all-cause mortality independent of CVD risk factors. The standard AAC score, the Agatston, up-weights for greater calcium density, and thus models higher calcium density as associated with increased CVD risk. We determined associations of CVD risk factors with AAC volume and density (separately). METHODS: In a multi-ethnic cohort of community living adults, we used abdominal computed tomography scans to measure AAC volume and density. Multivariable linear regression was used to determine the period cross-sectional independent associations of CVD risk factors with AAC volume and AAC density in participants with prevalent AAC. RESULTS: Among 1413 participants with non-zero AAC scores, the mean age was 65 ± 9 years, 52% were men, 44% were European-, 24% were Hispanic-, 18% were African-, and 14% were Chinese Americans (EA, HA, AA, and CA respectively). Median (interquartile range, IQR) for AAC volume was 628 mm3 (157-1939 mm3), and mean AAC density was 3.0 ± 0.6. Compared to EA, each of HA, AA, and CA had lower natural log (ln) AAC volume, but higher AAC density. After adjustments for AAC density, older age, ever smoking history, higher systolic blood pressure, elevated total cholesterol, reduced HDL cholesterol, statin and anti-hypertensive medication use, family history of myocardial infarction, and alcohol consumption were significantly associated with higher ln(AAC volume). In contrast, after adjustments for ln(AAC volume), older age, ever smoking history, higher BMI, and lower HDL cholesterol were significantly associated with lower AAC density. CONCLUSIONS: Several CVD risk factors were associated with higher AAC volume, but lower AAC density. Future studies should investigate the impact of calcium density of aortic plaques in CVD.

[Biochemical and morphological assessment of the functional state of the endothelium in reconstructive operations on the abdominal aorta in animal experiments].

The article deals with the analysis of biochemical and morphological alterations in the functional state of the endothelium of laboratory animals after a reconstructive surgical intervention on the abdominal aorta. These alterations were assessed at various terms following operative treatment in the comparison group and intact control group. The authors carried out of computer-assisted morphometry of the reconstruction zone on histological preparations for correct interpretation of the biochemical alterations and assessment of the correlation between the studied biochemical indices in blood and the arterial wall.

Assessment of atherosclerotic plaques in a rabbit model by delayed-phase contrast-enhanced CT angiography: comparison with histopathology.

The aim of this study was to compare delayed-phase computed tomography angiography (CTA) attenuation values with histopathology, in ability to differentiate between fibrous and lipid-rich plaques in an experimental rabbit model. Twelve atherosclerotic rabbits underwent CTA of the abdominal aorta. The scan protocol included early-phase scans (EP), delayed scans at 90 s after contrast injection (DP(90s)), delayed scans at 10 min after contrast injection (DP(10min)), and delayed scan with saline infusion (DP(Saline)). Plaque composition was analyzed by histopathology (% of lipid-rich, fibrous and macrophage areas) and CT attenuation values in Hounsfield units. Using histopathology as the reference standard (n = 119), the overall sensitivity, specificity and accuracy of 64-slice CTA for the detection of plaques was 59, 100 and 79% for the EP scans; 88, 100 and 94% for the DP(90s) scans; 81, 100 and 90% for the DP(10min) scans; and 53, 100 and 76% for the DP(Saline) scans. CT density measurements showed a substantial overlap between fibrous and lipid-rich plaques, and poor correlations with the percentage of macrophage areas in both fibrous and lipid-rich plaques (r = 0.408, and r = 0.333). In delayed-phase 64-slice CTA, DP(90s) images have the best diagnostic performance for the detection of aortic plaques.

Scan reproducibility of magnetic resonance imaging assessment of aortic atherosclerosis burden.

Subclinical atherosclerosis precedes the onset of clinical disease by many years. Noninvasive magnetic resonance imaging (MRI) offers the opportunity to visualize and quantify atherosclerotic plaque. However, the reproducibility of MRI measurements of abdominal and thoracic aortic atherosclerosis has not been reported. Electrocardiogram-gated, T2-weighted, turbo spin echo MRI of the descending thoracic and abdominal aorta was performed on 16 subjects, comprising 10 subjects with multivessel coronary artery disease (CAD) and 6 subjects without angiographic CAD. Three identical MRIs were performed on each subject, with subject repositioning between the second and third scans. Aortic anatomic and plaque measurements were performed in a blinded fashion. Fourteen subjects (88%) had MRI evidence of atherosclerotic plaque on at least one image. Slice plaque burden, plaque area, and plaque perimeter were greater in the CAD group (52% vs. 9%, p = 0.002; 264 vs. 18 mm2, p = 0.009; 159 vs. 15 mm, p = 0.006, respectively). Measurements of total aortic lumen area, lumen circumference, plaque area, and plaque perimeter correlated highly among the three scans (all r = 0.96, all p < 0.001). Measurements of slice-specific aortic lumen area and lumen circumference also correlated highly (all r = 0.98, all p < 0.001). Correlations of slice-specific plaque area and plaque perimeter were significant (all p < 0.001) but less robust (r = 0.62-0.85). These data demonstrate that MRI is a reproducible technique for assessing aortic anatomy and total aortic atherosclerosis, but increased slice density should be considered if serial evaluation of slice-specific data is desired.