T-LAK-cell-originated protein kinase (TOPK) is a PDZ-binding kinase (PBK) that was recently identified as a novel member of the mitogen-activated protein kinase (MAPK) family. It has been shown to play an important role in many cellular functions. However, its role in cardiac function remains unclear. Thus, we have herein explored the biological function of TOPK in myocardial ischemia/reperfusion (I/R) and oxidative stress injury in H9C2 cardiomyocytes. I/R and ischemic preconditioning (IPC) were induced in rats by 3-hour reperfusion after 30-min occlusion of the left anterior descending coronary artery and by 3 cycles of 5-min I/R. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in H9C2 cardiomyocytes. TOPK expression was analyzed by western blotting, RT-PCR, immunohistochemical staining, and immunofluorescence imaging studies. The effects of TOPK gene overexpression and its inhibition via its inhibitor HI-TOPK-032 on cell viability and Bcl-2, Bax, ERK1/2, and p-ERK1/2 protein expression were analyzed by MTS assay and western blotting, respectively. The results showed that IPC alleviated myocardial I/R injury and induced TOPK activation. Furthermore, H₂O₂ induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H₂O₂-induced oxidative stress injury in myocardiocytes, whereas overexpression relieved it. In addition, the ERK pathway was positively regulated by TOPK signaling. In conclusion, our results indicate that TOPK might mediate a novel survival signal in myocardial I/R, and that its effect on anti-oxidative stress involves the ERK signaling pathway.

We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2′-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity.

To explore the potential correlation between 10-year atherosclerotic cardiovascular disease (ASCVD) risk and depressive symptoms in a general population. A cross-sectional study involving 11,956 permanent residents of Liaoning Province in China ≥35 years of age was conducted. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) while 10-year ASCVD risk was calculated using the tool suitable for China. Males had significantly higher 10-year ASCVD risk than females (14.2 ± 10.7% vs. 9.3 ± 9.1%; P < 0.001) but lower PHQ-9 score (2.34 ± 3.13 vs. 3.63 ± 4.02; P < 0.001). The mean PHQ-9 score increased significantly with advancing 10-year ASCVD risk category in both males (from 2.03 to 2.61; P for trend < 0.001) and females (from 3.04 to 4.61; P for trend < 0.001), and the increasing trend was more apparent in females (P < 0.001). Pearson correlation analyses showed that 10-year ASCVD risk positively correlated with PHQ-9 score in both sexes (Ps < 0.001). In multivariate linear regression analyses adjusting for confounding risk factors, the independent associations of 10-year ASCVD risk with PHQ-9 score were all significant in the total (β = 2.61; P < 0.001), male (β = 1.64; P = 0.001), and female subjects (β = 3.71; P < 0.001). Further, the interaction analysis proved the impacts of 10-year ASCVD risk on PHQ-9 score were more apparent in females than males (Ps < 0.001). The 10-year ASCVD risk was positively associated with depressive symptoms in both males and females, which was more apparent in the latter. These findings provided some novel data about the value of 10-year ASCVD risk in estimating depressive symptoms.

To investigate the association between CHADS2 score, depressive symptoms, and quality of life in a large general population from China. A cross-sectional study of 11,956 permanent residents of Liaoning Province in China ≥ 35 years of age was conducted between January and August 2013 (response rate 85.3%). All participants completed a questionnaire, had a physical examination, and underwent blood examination. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9), while the quality of life (QoL) was measured using the World Health Organization Quality of Life Brief Scale (WHOQOL-BREF). With increasing CHADS2 score, the prevalence of depressive symptoms increased from 4.9 to 27.8% (P < 0.001), and all scores of WHOQOL-BREF decreased significantly (all Ps < 0.001). After adjusting for confounding risk factors, subjects with CHADS2 score ≥ 3 had higher risk of depressive symptoms than those with CHADS2 score = 0 (all Ps < 0.05). Also, CHADS2 score was negatively associated with all scores of WHOQOL-BREF (all Ps < 0.001). Furthermore, subjects with any item in CHADS2 had higher prevalence of depressive symptoms (all Ps < 0.001). Heart failure and stroke remained independently associated with depressive symptoms after adjusting for confounding risk factors and other items (Ps < 0.001), while heart failure, age ≥ 75 years, diabetes mellitus, and stroke were all independently negatively associated with the total score of WHOQOL-BREF (all Ps < 0.05). The CHADS2 score is significantly associated with depressive symptoms and impaired quality of life in the general population.