Association of heat shock protein polymorphisms with patient susceptibility to coronary artery disease comorbid depression and anxiety in a Chinese population

Background Coronary artery disease (CAD) is one of the severe diseases that threaten human health worldwide. In addition, the associated rate of comorbidity with depression and anxiety is extremely high. Heat shock proteins (HSPs) are a group of proteins that possesses cardiovascular and psychological protection properties. The objective of this study is to determine the association of the two most widely studied HSPs, namely, HSP70 and HSP90, with CAD comorbid depression and anxiety in a Chinese population. Methods A case-control study involving 271 CAD patients and 113 healthy individuals was conducted. The 271 CAD patients include individuals with (123) and without depression (148) and individuals with (57) and without anxiety (214). Ten single nucleotide polymorphisms (SNPs) for HSP70 and seven SNPs for HSP90 were selected and genotyped. Results Results revealed that the HSP70 rs10892958 C allele and HSP70 rs2236658 T allele were associated with a decreased risk of CAD (P < 0.05), whereas the G allele of the rs11218941 polymorphism was associated with an increased risk of CAD. The haplotype analysis results indicated that the haplotype TGGGC of the HSPA8 gene (coded the HSP70 family, rs4936770/rs4802/rs10892958/rs11218941/rs2236658) significantly increased the risk of CAD (P = 0.008). Among the patients with CAD, the carriers of the CC genotype for the HSP90 rs1042665 showed higher risks of anxiety than the carriers of another genotypes. However, no significant relationships were found among the CAD with depression and CAD without depression groups for the selected SNPs. These findings suggested that the genetic polymorphisms in the HSP gene, especially the HSPA8 of HSP70, contribute to CAD susceptibility and rs1042665 genetic polymorphisms might have an effect on the anxiety incidence among CAD patients

Melatonin Modulates Lipid Metabolism in Porcine Cumulus–Oocyte Complex via Its Receptors

Lipid is a crucial energy resource for mammalian oocyte. Melatonin could benefit the maturation of porcine oocyte in vitro, but the related mechanism is not elucidated yet. In the current study, methods to monitor lipid metabolism in single live oocytes were firstly established using probes (Lipi-Blue and Lipi-Green). It was observed that both lipid biogenesis and lipolysis occurred in maturing oocyte, but the general level of lipids dropped. Then maturing oocytes stained with probes were treated with melatonin or lipid metabolic-related inhibitors (triacsin C, rotenone, or etomoxir). The results showed that the lipid metabolism and maturation of porcine oocytes were all disrupted and that melatonin rescued the oocytes treated with triacsin C or rotenone, but not those treated with etomoxir. Further investigation demonstrated that cumulus cells are able to transfer lipids to oocytes via gap junctions. It was also observed that melatonin receptors exist in cumulus cells and are required for oocytes to maintain lipid metabolism. Meanwhile, the global gene expressing in cumulus cells was also modulated by melatonin, especially the genes related to antioxidants (SOD1, GPX1, GPX3, GPX4, PRDX2, and PRDX5), lipid metabolism (FABP3, FABP5, ACACB, TECR, etc.), and mitochondrial respiration (GPD1, ETFB, CYC1, and the genes of ATP synthase). Altogether the current research demonstrates that melatonin modulates lipid metabolism in maturing oocytes through its receptors in cumulus cells and benefits the developmental competence of oocytes

Cabozantinib, a Multityrosine Kinase Inhibitor of MET and VEGF Receptors Which Suppresses Mouse Laser-Induced Choroidal Neovascularization

Choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries and is particularly associated with age-related macular degeneration (AMD). Cabozantinib (CBZ) hinders the activation of multiple receptor tyrosine kinases involved in tumor angiogenesis, such as hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). We aimed to investigate the role and mechanism of CBZ in a mouse laser-induced CNV model. In zebrafish embryos, CBZ perturbed intersegmental vessel (ISV) formation without obvious neurodevelopment impairment. In the mouse laser-induced CNV model, phosphorylated hepatocyte growth factor receptor (p-MET) and phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2) were increased in the CNV region. CBZ intravitreal injection or oral gavage alleviated CNV leakage and the CNV lesion area without obvious intraocular toxicity, as well as disturbed the phosphorylation of MET and VEGFR2. Additionally, CBZ downregulated the expression of the hepatocyte growth factor (HGF) with no effect on the expression of the vascular endothelial growth factor (VEGF). CBZ downregulated HGF, p-MET, and p-VEGFR2 expressions in vitro, as well as inhibited the proliferation, migration, and tube formation of b-End3 cells. In summary, CBZ alleviates mouse CNV formation possibly via inhibiting the activation of MET and VEGFR2. The findings provide a novel potential therapy method for CNV patients