Apelin-13 attenuates cisplatin-induced cardiotoxicity through inhibition of ROS-mediated DNA damage and regulation of MAPKs and AKT pathways.

Platinum-based chemotherapy represents one of the most effective ways in combating human cancers. However, the cardiotoxicity subsequent severely limited its clinical application. Increased evidences indicate that oxidative stress plays a crucial role in the pathological process of platinum-induced cardiotoxicity. It is reported that apelin-13 a bioactive peptide has the scavenging capacity of free radical, and it has the potential to regulate the cardiovascular system. Hence, the potential of apelin-13 to antagonize cisplatin-induced cardiotoxicity was evaluated in H9c2 rat myocardial cells in vitro and in C57 mice in vivo. The results showed that cisplatin indeed caused DNA damage in H9c2 cells by promoting the accumulation of intracellular reactive oxygen species (ROS) and superoxide anion, which led to cell apoptosis and resulted in overt cardiotoxicity. However, apelin-13 pre-treatment effectively attenuated the cisplatin-induced ROS and superoxide anion generation, inhibited DNA damage, and suppressed the PARP cleavage and caspases activation. Further investigation revealed that apelin-13 blocked cisplatin-induced H9c2 cells apoptosis involving the regulation of MAPKs and PI3K/Akt signaling pathway. Importantly, apelin-13 co-treatment also significantly attenuated cisplatin-induced cardiotoxicity in vivo by inhibiting myocardial cells apoptosis and improving angiogenesis in mice heart. Taken together, our results suggest that the use of apelin-13 may be an effective strategy for antagonizing the cardiotoxicity-induced by platinum-based chemotherapy.

Long-term prognostic value of QRS score in patients with successfully recanalized coronary chronic total occlusion and construction of a predictive nomogram model.

BACKGROUND: Few studies have evaluated the prognostic value of QRS score in patients with coronary chronic total occlusion (CTO) after successful recanalization. METHODS: A total of 474 patients with successfully recanalized coronary CTO were finally included in our study and were followed up for 34.0±5.3months. They were divided into 3 groups: QRS score≥8, QRS score 4-7 and QRS score 0-3. The primary outcome was composite endpoint of major adverse cardiac and cerebral events (MACCEs). A predictive nomogram was established to predict prognosis for MACCEs, and the predictive accuracy of the nomogram was determined by concordance index. RESULTS: We found that QRS score correlated moderately with wall motion score index (WMSI) (r=0.551, p<0.001), left ventricular ejection fraction (LVEF) (r=-0.339, p<0.001) and coronary collateral circulation (CCC) (r=-0.569, p<0.001). During follow-up, patients with higher QRS score were observed to undergo poor prognosis. After multivariable adjustment, QRS score was still a significant independent predictor for MACCEs [(hazard ratio 1.28, 95% CI 1.18-1.39, p<0.001) in model 1,(hazard ratio 1.30, 95% CI 1.21-1.41, p<0.001) in mode2] and mortality[(hazard ratio 1.33, 95% CI 1.14-1.57, p<0.001) in model 1, (hazard ratio 1.49 , 95% CI 1.24-1.79, p<0.001) in model 2]. Moreover, the nomogram could more accurately predict 3-year MACCEs (c-index: 0.84). CONCLUSION: QRS score is a strong independent predictor of long-term prognosis in patients with coronary CTO successfully recancalized. The proposed nomograms can be used for the prediction of MACCE in this population.

[Effect of dexamethasone on osteopontin expression in the lung tissue of asthmatic mice].

OBJECTIVE: To study the correlation between airway inflammation and osteopontin (OPN) level in the lung tissue, and to study the effect of dexamethasone (DXM) on OPN expression. METHODS: Fifty mice were randomly divided into 5 groups: normal control, ovalbumin (OVA)-challenged asthma groups (OVA inhalation for 1 week or 2 weeks) and DXM-treated asthma groups (DXM treatment for 1 week or 2 weeks). The mice were sensitized and challenged with OVA to prepare mouse model of acute asthma. Alterations of airway inflammation were observed by haematoxylin-eosin staining. Serum level of OVA-sIgE was evaluated using ELISA. OPN expression in the lung tissue was located and measured by immunohistochemistry and Western blot respectively. OPN mRNA level in the lung tissue was detected by real-time PCR. RESULTS: The asthma groups showed more pathological changes in the airway than the normal control and the DXM-treated groups. Compared with the OVA-challenged 1 week group, the pathological alterations increased in the OVA-challenged 2 weeks group. The level of OVA-sIgE in serum increased in the asthma groups compared with the control and the DXM groups (P<0.01). Serum OVA-sIgE sevel increased more significantly in the OVA-challenged 2 weeks group compared with the OVA-challenged 1 week group (P<0.01). OPN protein and mRNA levels were significantly raised in the asthma groups compared with the normal control and the DXM groups (P<0.01), and both levels increased more significantly in the OVA-challenged 2 weeks group compared with the OVA-challenged 1 week group (P<0.01). CONCLUSIONS: The increased OPN expression in the lung tissue is associated with more severe airway inflammation in asthmatic mice, suggesting that OPN may play an important role in the pathogenesis of asthma. DXM can alleviate airway inflammation possibly by inhibiting OPN production.