Parkin overexpression reduces inflammation-mediated cardiomyocyte apoptosis through activating Nrf2/ARE signaling pathway.

Inflammation has been acknowledged as one of the pathological alterations in various cardiovascular disorders. Parkin has been found to be associated with mitochondrial protection. In the present study, we explored the influence of Parkin overexpression on cardiomyocyte induced by LPS-mediated inflammation response. Our results demonstrated that cardiomyocyte viability was reduced and apoptotic rate was increased upon LPS treatment, an effect that may be caused by cardiomyocyte oxidative stress. At the molecular levels, LPS treatment promoted ROS production, a result that was followed by a drop in the levels of anti-oxidants. Interestingly, Parkin overexpression significantly promoted cardiomyocyte survival and this cardioprotective was attributable to the anti-oxidative property. Parkin overexpression enhanced the expression of anti-oxidative factors such as GSH, SOD and GPX, resulting into depressed ROS production. Further, we found that Parkin modulated cellular anti-oxidative capacity through the Nrf2/ARE signaling pathway. This finding demonstrates that oxidative stress could be considered as the core of inflammation response. Further, therapeutic approaches targeting Parkin would improve cardiomyocyte anti-oxidative capacity through activating Nrf2/ARE signaling pathway.

Comparison of Magnetic Microbubbles and Dual-modified Microbubbles Targeted to P-selectin for Imaging of Acute Endothelial Inflammation in the Abdominal Aorta.

PURPOSE: Ultrasound molecular imaging (UMI) has potential to evaluate an inflammatory profile of endothelium. However, it is less successful in large arteries. This study compared magnetic microbubbles (MBs) selectively targeted to endothelial P-selectin and dual-targeting MBs in vitro and in vivo. PROCEDURES: MBs were modified with P-selectin antibody (MBPM) or isotype control antibody (MBCM) via a magnetic streptavidin bridge, and MBs were conjugated to P-selectin antibody (MBP) or both P-selectin antibody and PAA-sialyl Lewisx (MBD) via regular streptavidin linker. Adherence of MBs was determined by using a parallel plate flow chamber at variable shear stress (0.5-24 dyn/cm2). Adhesive and magnetic behaviors of MBs were analyzed at 4.0 dyn/cm2 or at a flow rate of 50 mm/s. Attachment of MBs to P-selectin was determined with contrast-enhanced ultrasound (CEU) imaging of murine abdominal aorta inflammation. The expression of P-selectin was assessed by immunohistochemistry. RESULTS: The adhesive efficacy of MBD was greater than MBP and MBCM, but lower than MBPM under all shear stress conditions (P < 0.05). The behaviors of fast-binding and rolling slow down were noted in MBD and MBPM; meanwhile, magnetic shifting of MBs centerline was presented in MBPM. Contrast video intensity (VI) from adhered MBPM to P-selectin of the inflammatory aorta was significantly higher than those from MBD and MBP (P < 0.05). CONCLUSIONS: MBPM may be a better molecular probe than MBD for detection of P-selectin on aorta with CEU, likely due to the shifting of axial distribution. Thus, it may improve the detection of the inflammatory profile on large arteries by UMI.

High molecular weight chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide for tumor-targeted magnetic resonance imaging.

Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors.

[Relationship between myocardial systolic, diastolic functions and perfusion in coronary artery stenosis].

OBJECTIVE: To evaluate the relationship between myocardial systolic, diastolic functions and perfusion in coronary artery stenosis using velocity vector imaging (VVI) and myocardial contrast echocardiography (MCE). METHODS: Stenoses in the anterior descending branch of the coronary artery were induced in 8 dogs. Before and after coronary artery stenosis, two-dimensional images of the left ventricular mastoid muscle section on the short axis at rest and in the peak dose of dobutamine were obtained for evaluation of VVI and MCE. The myocardial blood flow A.beta values, peak systolic strain rate (SRsys) and peak diastolic strain rate (SRdia) in the direction of the circumference of the short axis were measured. RESULTS: At rest, only severe coronary stenosis resulted in significantly lowered SRsys, SRdia and A.beta value of the stenotic bed compared to the values before the stenosis (-1.1-/+0.50 vs -1.62-/+0.50, 1.19-/+0.48 vs 1.75-/+0.51, 0.4-/+0.21 vs 0.80-/+0.47, P<0.05). In stress, SRsys, SRdia and A.beta value of the stenotic bed gradually decreased as coronary stenosis worsened (-4.31-/+1.14 vs -3.20-/+0.98 vs -1.18-/+0.64, 4.51-/+1.13 vs 3.39-/+0.98 vs 1.37-/+0.64. 3.54-/+1.95 vs 1.81-/+0.89 vs 0.82-/+0.42, P<0.05). Both at rest and in stress, good correlations were noted between SRsys and SRdia (r(rest)=0.88, r(stress)=0.96, P<0.01), between SRsys and the standard A.beta values (r(rest)0.56, r(stress)=0.71, P<0.01), and between SRdia and A.beta (r(rest)=0.57, r(stress)=0.72, P<0.01) in the direction of the circumference of the short axis. CONCLUSIONS: Using VVI and MCE, the changes in myocardial perfusion and the systolic and diastolic functions in the direction of the circumference can be observed dynamically. VVI may help assess the condition of myocardial perfusion by evaluating the systolic and diastolic function.