Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6

Background The relationship between inflammatory markers and the characteristics of coronary atherosclerosis plaques is uncertain. The aim of the present study was to evaluate the relationship between the characteristics of coronary atherosclerosis plaques and inflammatory markers such as high sensitivity C-reactive proteins （Hs-CRP） and interleukin-6 （IL-6）. Methods All patients suspected of having coronary heart disease （CHD） underwent Siemens 64-slice CT angiography （64-SCTA） to distinguish the quality of plaque of coronary artery lesions. Blood samples were taken to measure levels of serum Hs-CRP and IL-6 in different plaque groups and the control group and compared with the value of 64-SCTA for detection of coronary artery plaque. Results The sensitivity of detecting coronary artery plaque by 64-SCTA was 87.4%, the specificity was 87.1%, the positive predictive value was 82.2%, and the negative predictive value was 91.0%. Comparing the levels of serum Hs-CRP and IL-6 among plaque groups, the mean levels of serum Hs-CRP and IL-6 in three plaque groups were significantly higher than those in the control group （P 〈0.01）. The mean levels of serum Hs-CRP and IL-6 in the soft plaque group and mixed plaque group were significantly higher than those in hard plaque group （P〈0.01）. Plaque burden in the soft plaque group and mixed plaque group was significantly higher than in the hard plaque group （P 〈0.01）, but there was no statistical difference between the soft plaque group and mixed plaque group （P=-0.246）. There was a negative correlation between the CT scale and Hs-CRP and IL-6 levels in the soft plaque group （r= -0.621, P〈0.01, and r= -0.593, P 〈0.01 respectively）. There was a positive correlation between the plaque burden and Hs-CRP and IL-6 levels in the soft plaque group （r=0.579, P〈0.05 and r=0.429, P〈0.05 respectively）. Conclusions 64-SCTA is an effective way to distinguish the different quality of coronary atherosclerosis plaque. Serum Hs-CRP and IL-6 levels can be considered as the indexes to judge the degree of CHD and may reflect the activity of plaque in CHD patients. Thus it is important for clinical diagnosis and risk evaluation of acute coronary syndrome （ACS） patients.

Effects of MSCs on the progression of atherosclerosis plaque in ApoE-knockout mice

Background Immune inflammatory response is throughout the entire process of atherosclerosis （AS）. It was unclear whether the mechanism of mesenchymal stem cells （MSCs） transplantation for treatment of AS is involved with inflammation regulation in the plaque area. The aim of this study was to explore the effects of MSCs in the formation of atherosclerosis plaque in hypercholesterolemic apoliprotein （apo）E-/- mice. Methods ApoE-/- mice MSCs were isolated and identified. At 8 weeks of age, 30 male ApoE-/- mice were randomly divided into negative control group （Neg, n = 10）, positive control group （Pos, n = 10） and mesenchymal stem cells group （MSCs, n = 10）. MSCs were injected through caudal vein into the body of Pos and MSCs group. The plaque area of all subjects were compared, the percentage of CD4^＋CD25^＋Tregs in different tissues were analyzed by fluorescence activated cell sorter （FACS）, proliferation response of splenocytes to MSCs was detected and cytokines in the supernatant were determined by enzyme linked immunosorbent assay （ELISA）. Results Compared with controls, MSCs resulted in a significant decrease of latherosclerotic plaques size （P 〈 0.05）, and a significant increase of CD4^＋CD25^＋ regulatory T cells in spleen （P 〈 0.05）. Specific proliferation response of CD4^＋CD25^＋ regulatory T cells in splenocytes to MCSs was significantly suppressed, the superanant level of TGF-[3 and IL-10 in MSCs group were increased while IFN-γ/ decreased significantly. Conclusion MSCs play an important role in regulating the inflammatory response and significantly inhibit the formation of the atherosclerosis plaque in ApoE-/-mice.

CD137-CD137L signaling promotes angiogenesis in atherosclerosis plaque of mice through activating nuclear factor of activated T cells c1

Objective To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1(NFATc1).Methods Apolipoprotein E knock out mice were divided into the following groups:control group(n=5),CD137 activated group(n=5)and CD137 in-

Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells

Very small superparamagnetic iron oxide nanoparticles （VSOPs） rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging （MRI）. This study was performed to identify the uptake mechanisms of VSOPs into atherosclerotic plaques. Low-density lipoprotein receptor-deficient （LDLR^-/-） mice with advanced atherosclerosis were analyzed using MRI and transmission electron microscopy （TEM） at various time points after intravenous administration of VSOPs. Post-mortem MRI detected VSOP labeling of atherosclerotic plaques 10 min after injection, and the signal increased over the first 3 h. TEM revealed that the intensive plaque labeling was mediated by accelerated transcytosis of VSOPs through endothelial cells overlaying atherosclerotic lesions. Experiments with endocytosis inhibitors and small interfering RNA （siRNA） revealed a dynamin-dependent mechanism involving both clathrin- and caveolin-mediated processes. In cell culture experiments, endothelial VSOP uptake was enhanced under proatherogenic flow and TNFα stimulation, conditions that are both present in plaque areas. Our study demonstrates that VSOPs enable non-invasive MRI assessment of accelerated endothelial transcytosis, an important pathomechanism in atherosclerotic plaque formation.