Retraction Note: Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

This Article has been retracted.

Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

A rat model for chronic spinal nerve root compression.

OBJECTIVES: The pathophysiology of radiculopathy associated with lumbar spinal stenosis and lumbar disc herniation is incompletely understood. The goal of the present study was to establish a chronic spinal nerve root compression model that can mimic lumbar disc herniation or spinal stenosis using silicone tube compression. We also try to link the pathology changes of damaged nerve root with the reaction of microglia in spinal cord in same rat at different time points. METHODS: Thirty rats were used in this study. The L5 nerve roots (dorsal and ventral) were exposed by hemilaminectomy; the diameter of the L5 nerve root was measured at the 2 mm proximal from the dorsal root ganglia. The dorsal and ventral nerve roots of L5 were compressed using a silicone tube, and the sham group was only exposed dorsal and ventral roots of L5. Five rats from the sham group were perfused at 8 days after surgery, and 25 rats from the model groups were perfused at 3, 8, 12, 45 days, and 5 months after surgery, each model group was composed of 5 rats according to the time point. The L5 spinal cord segments and nerve root that compressed by silicone tube were harvested from the same rat. Microglia and neuron in the spinal cord were stained by immunohistochemistry, and the nerve root was shown by electron microscope. RESULTS: In sham-operated rat, the arrangement of axon and myelin sheath is normal, the ventral root is mainly composed of large axon (>6 µm) and it is composed of 46.3 % of all the axons of the ventral root; the average myelin thickness of large axon is 1.86 µm; the dorsal root is mainly composed of medium (2-3.9 or 4-5.9 µm) axons and they are composed of 79.1 % of all the axons of the dorsal root; the average myelin thickness of this category is 0.94 or 1.55 µm. The average myelin thickness of large axon in ventral root reduced to 0.97 and 1.19 µm from more than 1.86 µm after compression for 3 and 8 days separately. Most of myelin sheath disappeared after 12 days of compression; the myelin sheath was partly restored at 45 days after compression which the myelin sheath thickness of large axons in ventral root was 0.47 µm. The medium category in dorsal root reduced to 0.59 or 0.72 µm from 0.94 µm, and 1.55 µm after compression for 3 days (p < 0.05 to p < 0.0001). The medium category axon in dorsal root is also 0.47 µm after compression for 45 days (p ≤ 0.0001). The myelin sheath was almost totally restored at the 5 months of compression; the myelin sheath thickness returned to normal and the axons were intact in structure under EM. The number of Iba1-positive microglia increased by 18.69, 40.44, and 18.49 % after compression for 3, 8, and 12 days separately in the ipsilateral dorsal horn and 21.26, 32.15, 22.87 % in ventral horns, and the activation of microglia was also prominent in contralateral sides of the dorsal and ventral horn at 8 days time point. The microglia cell reconverted to resting status after compression for 45 days or 5 months. CONCLUSION: The chronic spinal nerve root compression with silicone tube produces a recoverable damage to nerve root, which produces recoverable microglial activation in the spinal cord. These results demonstrated that the chronic spinal nerve root compression with silicone tube could mimic the pathological changes of lumbar spinal stenosis or lumbar disc herniation.

Reference values for vertebral shape in young Chinese women: implication for assessment of vertebral deformity.

The race- and sex-specific reference values for vertebral shape are important to determine the prevalence of osteoporotic vertebral fracture. However, these reference values are absent in Chinese women. In the present study, the anterior, middle and posterior heights and the ratios of these heights were measured from 14 vertebral bodies (T4-L5) in 60 premenopausal Chinese women (aged 19-25 years). Cutoff values were set as standard deviations (3 and 3.5 SD) and percentages (15 and 20%) below the means of vertebral height (VH) ratios to define vertebral deformities. The number of subjects with a VH ratio lower than -15% cutoff were significantly more than those with a VH ratio lower than -3 SD cutoff (p < 0.05), but this difference did not occur when a -20% cutoff was selected. A few VH ratios were distributed below -20% and -3 SD cutoffs, and none was below -3.5 SD. The vertebral shape defined by VH ratios was different between Chinese and European women. We conclude that 3.5 SD below the reference mean is an ideal cutoff value for the definition of prevalent vertebral fractures in Chinese women, and reference data should be obtained from young premenopausal women.

[EphrinB2 gene transfection promotes the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells].

OBJECTIVE: To study the effects of ephrinB2 gene transfection on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into vascular endothelial cells. METHODS: Wistar rat BMSCs were isolated by density gradient centrifugation and purified on the basis of their adhesion ability. The BMSCs were transfected with a lenti-virus vector encoding a constitutively active form of human ephrinB2 gene, and the cell markers including CD105, CD73, CD44, von Willebrand factor (VWF) and vascular growth factor receptor 2 (KDR) were detected using flow cytometry. The potential of ephrinB2-BMSCs for differentiation into osteoblasts and adipoblasts in vitro were tested, and the differentiation of the cells into endothelial-like cells was induced by culture in the presence of 2% fetal bovine serum and 50 ng/ml vascular endothelial growth factor. RESULTS: EphrinB2-BMSCs were positive for the markers CD105, CD73 and CD44, and negative for the typical endothelial markers like VWF and KDR, and retained high potentials for differentiation into osteoblasts and adipoblasts in vitro after cultivation in respective media. After induced differentiation, ephrinB2-BMSCs expressed VWF and KDR and showed greater ability of differentiation into vascular endothelial cells and formation of capillary structures on matrix gel than the BMSCs without transfection. CONCLUSIONS: EphrinB2 gene transfection efficiently promotes the differentiation of BMSCs into vascular endothelial cells. These genetically engineered cells provide valuable sources for new therapies of coronary heart disease.

[Comparative study on effects of puerarin and granulocyte colony-stimulating factor in treating acute myocardial infarction].

OBJECTIVE: To compare the effects of puerarin and granulocyte colony-stimulating factor (G-CSF) in treating acute myocardial infarction (AMI) and on the size of infarcted area and cytokines. METHODS: Seventy-nine patients with anterior AMI were randomly divided into three groups, they were treated with conventional Western medical treatment, but to the puerarin group (PG) and the G-CSF group (GCG) puerarin and G-CSF was given additionally, respectively. The infarcted size, plasma G-CSF, matrix metalloproteinase-9 (MMP-9), serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected before and after treatment. RESULTS: The infarcted size was positively correlated to the levels of G-CSF, MMP-9, IL-6 and TNF-alpha before treatment ( r = 0.45, 0.42, 0.44 and 0.42, P<0.01 ). The infarcted size in the PG and the GCG decreased on the 28th day (P<0.01), the level of G-CSF, MMP-9, IL-6 and TNF-alpha in the PG on the 7th day all decreased (P<0.05), but these indexes in the GCG increased (P<0.05), while those in the control group were unchanged (P>0.05). CONCLUSION: Puerarin and G-CSF are effective in decreasing infarcted size, but their effects on cytokines are different entirely.

[Effects of carvedilol on neurohormone and magnesium metabolism in patients with chronic heart failure].

OBJECTIVE: To investigate the effects of carvedilol on neurohormone and magnesium metabolism in patients with chronic heart failure (CHF). METHODS: Fifty-seven patients with CHF were divided into two groups randomly: received conventional treatment alone or combined with carvedilol for 8 weeks, respectively. Urine magnesium excretion (UME), plasma levels of magnesium (PMC), norepinephrine (NE), angiotensin-II (Ang-II), aldosterone (ALD), plasma renin activity (PRA) and peripheral monocyte magnesium content (MMC) were measured before and after treatments. Twenty-six health persons were selected as normal subjects. RESULTS: There was a significant increase in UME and plasma concentrations of NE, ALD, Ang-II and PRA, and a significant decrease in MMC in patients with CHF, compared with the control group (P < 0.01). UME was positively correlated with ALD, Ang-II, PRA r = 0.41, 0.42, 0.38, respectively (P < 0.01). These parameters significantly improved after carvedilol (P < 0.05). CONCLUSION: Carvedilol decreases significantly plasma concentrations of neurohormone and urine magnesium excretion, and increases cell magnesium content in patients with CHF.