HPV11 E6 mutation by overexpression of APOBEC3A and effects of interferon-ω on APOBEC3s and HPV11 E6 expression in HPV11.HaCaT cells.

BACKGROUND: Condyloma acuminatum, infected by low-risk human papillomaviruses (e.g., HPV6 and HPV11), is one of the most widespread sexually transmitted diseases. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 proteins (APOBEC3s, A3s) are cellular cytidine deaminases acting as antiviral factors through hypermutation of viral genome. However, it remains unknown whether A3s results in HPV11 gene mutations and interferon-ω (IFN-ω) exhibits antiviral activities through the A3s system. Here we investigated whether enhanced APOBEC3A (A3A) resulted in the E6 gene mutations and explore the effects of recombinant human interferon-ω (rhIFN-ω) on A3s/E6 expression in HaCaT keratinocytes containing the genome of HPV 11 (HPV11.HaCaT cells). METHODS: A3A-overexpressed HPV11.HaCaT (A3A-HPV11.HaCaT) cells were established by lentiviral infection and verified by immunofluorescence and western-blotting. Cell cycle, E6 gene mutations, APOBEC3s/E6 gene expression and subcellular localization were detected by FACS, 3D-PCR and sequencing, qRT-PCR and immunofluorescence respectively. RESULTS: The results suggested that A3A-HPV11.HaCaT cells were successfully established. Enhanced A3A induced S-phase arrest, G > A/C > T mutations and obvious reduction of E6 mRNA expression. A3A/A3B mRNA expression was up-regulated at 6 h and 12 h and obvious A3A staining existed throughout HPV11.HaCaT cells after rhIFN-ω treatment. RhIFN-ω could also inhibit mRNA expression of HPV11 E6 significantly. CONCLUSIONS: Enhanced A3A repressed HPV11 E6 expression through gene hypermutation, and rhIFN-ω might be an effective agent against HPV11 infection by up-regulation of A3A.

Characteristics of myocardial postsystolic shortening in patients with symptomatic hypertrophic obstructive cardiomyopathy before and half a year after alcohol septal ablation assessed by speckle tracking echocardiography.

OBJECTIVES: Postsystolic shortening (PSS) has been proposed as a marker of myocardial dysfunction. Percutaneous transluminal septal myocardial ablation (PTSMA) is an alternative therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) that results in sustained improvements in atrial structure and function. We investigated the effects of PTSMA on PSS in HOCM patients using speckle tracking imaging. METHODS: Conventional echocardiographic and PSS parameters were obtained in 18 healthy controls and 30 HOCM patients before and half a year after PTSMA. RESULTS: Compared with the healthy controls, the number of segments having PSS and the average value of PSS were significantly increased in the HOCM patients. At 6 months after PTSMA, both the number of segments having PSS (10.5±2.8 vs. 13.2±2.6; P<0.001) and the average value of PSS (-1.24±0.57 vs. -1.55±0.56; P = 0.009) were significantly reduced. Moreover, the reductions in the average value of PSS correlated well with the reductions in the E-to-Ea ratio (r = 0.705, P<0.001). CONCLUSIONS: Both the number of segments having PSS and the average value of PSS were significantly increased in the HOCM patients. PTSMA has a favourable effect on PSS, which may partly account for the persistent improvement in LV diastolic function in HOCM patients after PTSMA.

Evaluation of left ventricular diastolic function by global strain rate imaging in patients with obstructive hypertrophic cardiomyopathy: a simultaneous speckle tracking echocardiography and cardiac catheterization study.

BACKGROUND: Impaired left ventricular (LV) diastolic function is a common pathophysiological feature of patients with hypertrophic cardiomyopathy (HCM). The noninvasive evaluation of diastolic function in these patients remains a challenge. Speckle tracking echocardiography (STE) provides direct information on intrinsic myocardial function and may improve the diagnostic of diastolic dysfunction in HCM patients. METHODS AND RESULTS: We retrospectively analyzed 51 patients with obstructive HCM (HOCM). Strain rate (SR) curves were obtained for 18 different segments of the LV myocardium. The peak SR during the isovolumic relaxation period (SRIVR ) and the peak early diastolic strain rate (SRE ) were measured for each segment. Cardiac catheterization was performed within 24 hours after echocardiographic analysis. LV end-diastolic pressure (LVEDP) was measured and time constant of myocardial relaxation (τ) was calculated. We therefore correlated STE-derived with invasive indices and compared it with flow and tissue Doppler measurements. SRIVR and SRE were significantly reduced in all 51 HOCM patients (0.16 ± 0.09%/sec and 0.71 ± 0.25%/sec).The ratio of peak early mitral inflow velocities to SRIVR and SRE (E/SRIVR and E/SRE ) correlated well with LVEDP (r = 0.760, P < 0.001; r = 0.401, P = 0.004). Receiver operating characteristic analysis shown E/SRE ratio had the largest under curve area in predicting HOCM patients with seriously elevated LVEDP. In addition, SRIVR and SRE significantly related with τ (r = -0.611, P < 0.001; r = -0.369, P = 0.008). CONCLUSIONS: Diastolic function was seriously impaired in HOCM patients. The E/SRE ratio can be used to predict LVEDP with acceptable accurate in HOCM patients. In addition, SRIVR is a reliable parameter to assess LV relaxation in patients with HOCM.

Effect of septal ablation on regional diastolic dysfunction and diastolic asynchrony in patients with hypertrophic obstructive cardiomyopathy: a follow-up study using speckle tracking echocardiography.

BACKGROUND: Percutaneous transluminal septal myocardial ablation (PTSMA) is an alternative therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) that results in sustained improvement in the global diastolic dysfunction. Regional diastolic abnormalities and diastolic asynchrony are very common and closely related to global diastolic dysfunction. The aim of this study was to examine the effect of PTSMA on regional diastolic dysfunction and diastolic asynchrony in HOCM patients using speckle tracking echocardiography. METHODS: Strain rate curves were obtained for 18 different segments of the left ventricular (LV) myocardium in 30 HOCM patients 24 hours before and 1 year after PTSMA. The peak strain rate during the isovolumic relaxation period (SRIVR ), the peak early diastolic strain rate (SRE ), and the time from the onset of the QRS-wave to SRE (TSRE ) were measured for each segment. The left atrial volume indexed to the body surface area (LAVI) was measured as a global diastolic index. RESULTS: At 1 year after PTSMA, there was significant improvement of the global SRIVR (0.14 ± 0.06-0.22 ± 0.07%/sec, P < 0.001) and SRE (0.67 ± 0.24-0.82 ± 0.23%/sec, P = 0.001). The coefficient of variation in TSRE (CVTSRE ) decreased significantly. The changes in the regional myocardial diastolic deformation and CVTSRE correlated well with the reduction in the LAVI. CONCLUSIONS: Percutaneous transluminal septal myocardial ablation has a favorable effect on regional diastolic abnormalities and diastolic asynchrony, which may partly account for the persistent improvement in global LV diastolic function in HOCM patients after PTSMA.

Assessment of atrial conduction abnormalities in patients with hypertrophic cardiomyopathy before and one year after alcohol septal ablation.

OBJECTIVES: Intra- and interatrial electromechanical delay (AEMD) can be used to evaluate the development of atrial fibrillation (AF). Percutaneous transluminal septal myocardial ablation (PTSMA) is an alternative therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) that results in sustained improvements in atrial structure and function. We investigated the effects of PTSMA on the intra- and inter-AEMD of HOCM patients using tissue Doppler imaging. METHODS: Conventional echocardiographic and AEMD parameters were obtained in 25 healthy controls and 31 HOCM patients before and 1 year after septal ablation procedures. RESULTS: Compared with the healthy controls, the left atrial volumes indexed by body surface area (LAVI) and the intra- and inter-AEMD were significantly higher in the HOCM patients. At 1 year after PTSMA, the LAVI was decreased (37.2 ± 11.4 to 27.0 ± 8.5 ml/m(2), p < 0.001). The intra- and inter-AEMD were also significantly decreased (22.7 ± 9.2 to 16.6 ± 7.7 ms, p < 0.001 and 37.0 ± 8.4 to 26.6 ± 8.0 ms, p < 0.001, respectively). These changes correlated well with the reductions in LAVI (r = 0.83, p < 0.001; r = 0.66, p < 0.001). CONCLUSIONS: Both the intra- and inter-AEMD were significantly prolonged in the HOCM patients. PTSMA can improve the prolonged and inhomogeneous propagation of sinus impulses in atria.

Different impacts of C-reactive protein and lipid profile on coronary lesions following a percutaneous coronary intervention.

OBJECTIVE: In-stent restenosis (ISR) and lesion progression are major obstacles for a percutaneous coronary intervention (PCI). Although previous studies have suggested that inflammation and lipid profile may be involved in those pathophysiological events, it remains controversial to date. The aim of the present study was to investigate the impacts of inflammation and lipid profile on both ISR and lesion progression in patients receiving PCI and scheduled follow-up. METHODS: A retrospective analysis of 513 patients was performed in patients who underwent PCI and received coronary angiography again at an average of 7 months. The data of lipid profile and C-reactive protein (CRP) at both pre-PCI and follow-up were analyzed in patients with 94 ISR group and 65 lesion progression (progression group) alone, which was compared with 307 patients with neither ISR nor lesion progression (control group). RESULTS: CRP levels at pre-PCI in the ISR group were higher than those in the control group (P<0.05). The multivariate analysis indicated that the CRP levels at both pre-PCI and follow-up were significantly correlated with ISR [odds ratio (OR)=1.095, 95% confidence interval (CI) 1.005-1.194 for pre-PCI, OR=1.156, 95% CI 1.054-1.267 for follow-up, P<0.05, respectively]. When the cut-off of CRP was 2 mg/l, logistic regression analysis suggested an increased risk of ISR in patients with greater than 2 mg/l (OR=1.89, 95% CI 1.031-3.465) at pre-PCI CRP. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) at follow-up in the progression group were higher than those in the control group (P<0.05, respectively). Logistic regression showed that the risk for lesion progression was associated with the concentrations of TC, LDL-C, and non-HDL-C (P<0.05). CONCLUSION: The levels of pre-PCI CRP were strongly associated with ISR, whereas diabetes, serum levels of TC, LDL-C, and non-HDL-C were significantly correlated with coronary lesion progression.

[Different effects of inflammation and lipid levels on coronary lesions after PCI].

OBJECTIVE: To assess the different effects of inflammation and lipid levels before and after PCI on in-stent restenosis and lesion progression. METHODS: Patients were studied who successfully underwent PCI with stent implantation and were received coronary angiography again after three months to one year. In-stent restenosis was observed in 94 patients and lesion progression in 65 patients. No restenosis and lesion progression occurred in 307 cases. Total cholesterol (TC), total triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), C reactive protein (CRP) and high sensitive CRP (hsCRP) were determined before PCI and at time of re-angiography. RESULTS: The levels of CRP and hsCRP before PCI in restenosis group were higher than those with no restenosis (CRP: median = 3.61 mg/L and 2.86 mg/L respectively, hsCRP: median = 1.56 mg/L and 0.89 mg/L respectively, P < 0.05). There was also difference between two groups in CRP levels at post-PCI follow-ups (median = 1.92 mg/L and 1.14 mg/L respectively, P < 0.05). The rate of restenosis in patients with hsCRP > 2 mg/L before PCI was higher than that in patients with hsCRP < or = 2 mg/L (Chi(2) = 4.32, P < 0.05). Logistic regression showed that the risk of restenosis markedly increased in patients with hsCRP > 2 mg/L (OR = 1.89, 95% CI 1.031-3.465). During the follow-up angiography the levels of TC, LDL-C and non-HDL-C were higher in lesion progression group than those in control group [TC (4.62 +/- 1.14) mmol/L and (4.26 +/- 1.01) mmol/L, LDL-C (2.51 +/- 0.93) mmol/L and (2.25 +/- 0.75) mmol/L, non-HDL-C (3.52 +/- 1.12) mmol/L and (3.20 +/- 0.98) mmol/L, respectively, P < 0.05). CONCLUSION: Inflammation state before and after PCI are the risk factors for in-stent restenosis, while the levels of TC, LDL-C and non-HDL-C are the important risk factors for other coronary lesion progression. Secondary prevention should be long-term emphasized and strengthened after PCI.