Xumin Guan

Protection against doxorubicin-induced myocardial dysfunction in mice by cardiac-specific expression of carboxyl terminus of hsp70-interacting protein

Carboxyl terminus of Hsp70-interacting protein (CHIP) is a critical ubiquitin ligase/cochaperone to reduce cardiac oxidative stress, inflammation, cardiomyocyte apoptosis and autophage etc. However, it is unclear whether overexpression of CHIP in the heart would exert protective effects against DOX-induced cardiomyopathy. Cardiac-specific CHIP transgenic (CHIP-TG) mice and the wild-type (WT) littermates were treated with DOX or saline. DOX-induced cardiac atrophy, dysfunction, inflammation, oxidative stress and cardiomyocyte apoptosis were significantly attenuated in CHIP-TG mice. CHIP-TG mice also showed higher survival rate than that of WT mice (40% versus 10%) after 10-day administration of DOX. In contrast, knockdown of CHIP by siRNA in vitro further enhanced DOX-induced cardiotoxic effects. Global gene microarray assay revealed that after DOX-treatment, differentially expressed genes between WT and CHIP-TG mice were mainly involved in apoptosis, atrophy, immune/inflammation and oxidative stress. Mechanistically, CHIP directly promotes ubiquitin-mediated degradation of p53 and SHP-1, which results in activation of ERK1/2 and STAT3 pathways thereby ameliorating DOX-induced cardiac toxicity.

Higher High-Sensitivity C Reactive Protein is Associated with Future Premature Ventricular Contraction: a Community Based Prospective Cohort Study

We aimed to determine whether hs-CRP is a predictor of future premature ventricular contraction (PVC) events in a community based population. A total of 101,510 participants were recruited at baseline (2006–2007). The follow-up visits were conducted every two years. Participants who were free from PVC at baseline and achieved the fourth visit, or diagnosed of PVC during the subsequent visits were included for analyses. Diagnosis of PVC was based on standard supine resting, 10-s 12-lead ECG. Cox regression was applied to evaluate the association between quartiles of hs-CRP and the incidence of PVCs. 60710 participants (male: 79.9%, mean age 49.4 years) were included for analyses. During a mean follow-up of 74.9 ± 7.4 months, 908 (1.5%) participants were diagnosed with PVC. Participants of the highest quartile of hs-CRP had significantly increased risk of PVC events as compared with the lowest quartile (HR 1.36; 95% CI 1.12–1.66); and stratified analyses showed similar result in males (HR 1.45; 95% CI 1.16–1.80), but not in females (HR 1.12; 95% CI 0.71–1.79). Moreover, elevated serum hs-CRP was associated with future PVC in participants without history of myocardial infarction or stroke (HR 1.34; 95% CI 1.09–1.65). Elevated hs-CRP was an independent predictor of PVC in Chinese population, especially in men.

Atrial fibrillation is related to lower incidence of deep venous thrombosis in patients with pulmonary embolism

Background Atrial fibrillation (AF) is an established risk factor of left atrial thrombosis and systemic embolism. Traditionally pulmonary embolism (PE) is a recognized complication of deep vein thrombosis (DVT). However, whether AF is responsible for right atrial thrombosis and leads to PE has not been examined. Methods We retrospectively analyzed medical records of patients with confirmed diagnosis of PE with AF (study group) from 2002-2015. Patients with PE without AF, matched by age and sex, served as controls (control group). The CHA2DS2-VASc and CHADS2 scores were classified into two categories, low-intermediate (<2 points) and high-risk (≥2 points). Results A total of 330 patients (110 in study group and 220 in control group). The study group had significantly lower incidence of newly diagnosed DVT (21% vs. 44%, P<0.001), previous history of DVT (6% vs. 17%, P=0.006) and recent surgery or trauma (10% vs. 23%, P=0.004) compared to the control group. When stratified by the CHADS2 score, 49 patients (44.5%) were considered low-intermediate risk. This proportion significantly differed when stratified using CHA2DS2-VASc, in which 13 patients (13.6%) were considered low-intermediate risk, P<0.001. Conclusions The incidence of DVT was much lower in the study group, suggesting the possibility of clots originated from the right heart that may increase the risk of PE. The CHA2DS2-VASc scoring system might be more sensitive for prediction and stratification of the PE in AF patients than the CHADS2 score.

Association of Total Cholesterol, Low-Density Lipoprotein Cholesterol, and Non-High-Density Lipoprotein Cholesterol with Atherosclerotic Cardiovascular Disease and Cancer in a Chinese Male Population

This prospective study included 68,759 Chinese male adults from Kailuan cohort of China who had a standardized medical examination between 2006 and 2007 and were followed up for approximately 8 years until occurrence of ASCVD, cancer or death or until December 31, 2014. Subjects were divided into four categories based on the quartiles of TC, LDL‐C and non‐HDL‐C. Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). During follow‐up, 2,916 males developed ASCVD and 1,884 developed cancer. Compared with the lowest quartile, the upper‐most quartiles of TC, LDL‐C and non‐HDL‐C were all associated with increased ASCVD risk (HR 1.53; HR 1.16; HR 1.55); however, the upper‐most quartiles of TC, LDL‐C and non‐HDL‐C were all negatively associated with cancer (HR0.84; HR 0.82; HR 0.80) and these associations were present after exclusion of incident cancers during the first 4 years of follow‐up. In a word, we report that high TC, LDL‐C and non‐HDL‐C concentrations increased ASCVD incidence in a male population and that these lipid profiles were inversely associated with total cancer and several individual cancers.

Lipid profile and incidence of atrial fibrillation: A prospective cohort study in China

The association between dyslipidemia, a major risk factor for cardiovascular diseases, and atrial fibrillation (AF) is not clear because of limited evidence.