Targeting the Ferroptosis and Endoplasmic Reticulum Stress Signaling Pathways by CBX7 in Myocardial Ischemia/reperfusion Injury.

Ferroptosis and endoplasmic reticulum stress (ERS) are common events in the process of myocardial ischemia/reperfusion injury (IRI). The suppression of chromobox7 (CBX7) has been reported to protect against ischemia/reperfusion injury, This research is purposed to expose the impacts and mechanism of CBX7 in myocardial IRI. CBX7 expression was detected using RT-qPCR and western blotting analysis. CCK-8 assay detected cell viability. Inflammatory response and oxidative stress were detected by ELISA, DCFH-DA probe and related assay kits. Flow cytometry analysis and caspase3 activity assay were used to detect cell apoptosis. C11-BODIPY 581/591 staining and ferro-orange staining were used to detect lipid reactive oxygen species (ROS) and Fe2+ level, respectively. Western blotting was used to detect the expression of proteins associated with apoptosis, ferroptosis and ERS. In the hypoxia/reoxygenation (H/R) model of rat cardiomyocytes H9c2, CBX7 was highly expressed. CBX7 interference significantly protected against inflammatory response, oxidative stress, apoptosis, ferroptosis and ERS induced by H/R in H9c2 cells. Moreover, after the pretreatment with ferroptosis activator erastin or ERS agonist Tunicamycin (TM), the protective effects of CBX7 knockdown on the inflammation, oxidative stress and apoptosis in H/R-induced H9c2 cells was partially abolished. To summarize, CBX7 down-regulation may exert anti-ferroptosis and anti-ERS activities to alleviate H/R-stimulated myocardial injury.

Relationship between RAGE gene polymorphisms and cardiovascular disease prognosis in the Chinese Han population.

Cardiovascular disease (CVD) is the leading cause of death in China. This study aimed to investigate whether RAGE gene polymorphisms are associated with the prognosis of various cardiovascular diseases in the Chinese Han population. This study was conducted from July 2004 to December 2005 and a total of 425 subjects from Guangdong province were enrolled. Genotyping of the three polymorphisms (-429T/C, 1704G/T, and G82S) in the RAGE gene was performed with polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 6.5 years to watch for the development of cardiovascular events and mortality. Subjects with the S mutation of the G82S polymorphism had a significantly higher risk of all-cause mortality and acute myocardial infarction (AMI) than did those with wild-type homozygosity. Logistic regression analysis and Kaplan-Meier analysis all revealed that the G82S polymorphism of the RAGE gene was associated with a significantly increased risk of all-cause mortality and AMI. However, the -429T/C and 1704G/T polymorphisms were not shown to have any effect on prognosis. In conclusion, the G82S variant of the RAGE gene was significantly associated with an increased risk of all-cause mortality and AMI in the Chinese Han population.

Effect of obstructive sleep apnea syndrome on serum C-reactive protein level, left atrial size and premature atrial contraction.

OBJECTIVE: To assess the changes of serum C-reactive protein (CRP) level, left atrial size and atrial premature contraction (PAC) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: This study involved 277 patients with OSAS diagnosed after an overnight polysomnography, who underwent a 24-h Holter electrocardiography and ambulatory blood pressure monitoring for detection of PAC. According to the apnea-hypopnea index (AHI), 137 patients with PAC identified from these patients were classified into 3 groups, namely the mild (5≥AHI<15), moderate (15≥AHI<30) and severe (AHI≥30) groups. Serum CRP level was assessed by a high-sensitivity radio-immunoassay. The left atrial diameter and echocardiographic parameters were recorded by transthoracic Doppler echocardiography (TTE). RESULTS: We found a high prevalence of PAC in these OSAS patients (137/277, 49.4%). Serum CRP was significantly higher in severe OSAS group (5.01∓4.68 mg/L) than in the moderate (3.03∓1.94 mg/L) and mild OSAS (2.98∓1.82 mg/L) groups (P=0.040 and 0.033, respectively). The left atrial diameter was significantly increased in severe OSAS group (40.1∓7.9 mm) as compared to that in moderate (37.9∓5.5 mm) and mild (33.7 ∓ 3.8 mm) groups (P=0.025 and 0.002, respectively). The severity of OSAS was positively correlated to both CRP (r=0.304, P=0.034) and left atrial diameter (r=0.411, P=0.003). After adjusting for gender, age and body mass index (BMI), a strong correlation was found between the left atrial diameter and CRP (r=0.594, P=0.0005). CONCLUSION: There is a high prevalence of PAC in OSAS patients. The progression of OSAS is associated with increased serum CRP level and left atrial size in patients with premature atrial complexes. Our study suggests that inflammation associated with OSAS might contribute to atrial structural and electrical remodeling in OSAS patients with PAC.