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.

The beneficial effects of exercise on glucose and lipid metabolism during statin therapy is partially mediated by changes of the intestinal flora.

Recent research has confirmed that moderate-intensity exercise affects the gut microbiome composition and improves cardiac function in an animal model after myocardial infarction (MI). However, few studies have investigated the effects of exercise on glucose and lipid metabolism in patients with coronary heart disease (CHD) receiving a statin treatment and successful percutaneous coronary intervention (PCI). Meanwhile, since statin therapy may lead to the risk of an increase in blood glucose level in CHD patients, we hypothesized that moderate-intensity exercise may be helpful for regulating glucose-lipid metabolism and stabilizing the blood glucose level in CHD patients. Therefore, to confirm our conjecture, we conducted a clinical retrospective study and animal experiment, respectively. The clinical study involved a total of 501 statin-treated patients with CHD after PCI. According to the study protocol, patients were divided into the following three groups: a non-exercise group, exercise at the recommended standard group, and exercise not at the recommended standard group. We found that qualified moderate-intensity exercise decreased blood glucose and lipid levels at follow-up at a mean of 2.2 years, and the incidence of new-onset diabetes showed a downward trend compared with the non-exercise and exercise not at the recommended standard groups. Furthermore, we used a high-fat rat model to explore an additional mechanism of the beneficial effects of exercise-based management on glucose-lipid metabolism apart from the known mechanism. We used 16S rRNA high-throughput sequencing technology to analyze the changes induced by exercise in the composition of intestinal flora in experimental rats. We found that rats that exercised with or without statin administration had lower plasma glucose and lipid levels and that these parameters were higher in the control and statin-treated rats that did not exercise. These results were consistent with the human study. The results from high-throughput sequencing of the intestinal flora of rats showed, to the best of our knowledge, that exercise leads to an increased relative abundance of Akkermansia muciniphila, which contributes to improved glucose and lipid metabolism. Based on our current results, we suggest that moderate-intensity exercise can improve glucose and lipid metabolism and prevent statin treatment-related side effects, such as hyperglycemia, in patients after PCI. Exercise could facilitate the applicability of statins for lower lipid levels. Exercise training also provides additional benefits, such as alteration of the gut microbiota, which contributes to improved glucose and lipid metabolism.

The gut microbiota is associated with clinical response to statin treatment in patients with coronary artery disease.

BACKGROUND: The structure and composition of the gut microbiota influence patients' response to therapeutic interventions. It is also known that the response to statin treatment can vary greatly from one patient to another, suggesting a possible connection between microbiome composition and response to statins. In the present study, we aim to explore the influence of the microbiome composition on the response to statin treatment among patients with coronary artery disease (CAD). METHODS: A prospective cohort of 836 CAD patients enrolled from January 2016 to December 2017 was used to perform a nested case-control study. We divided 110 CAD patients into two groups according to their response to statins (good response group and poor response group) and compared their gut microbiota. RESULTS: Our analysis reveals no significant difference in microbiome between the two groups. However, significant differences were found in the relative proportion of numerous genera between GR and PR groups. Most remarkably, we could observe that a poor response to statin treatment correlates to a significant decrease in the abundance of beneficial bacteria for the lipid metabolism (Akkermansia muciniphila (A. muciniphila) and Lactobacillus) and a significant increase in the abundance of bacteria (Holdemanella and Facecallibacterium). CONCLUSIONS: Gut microbiota structure is associated with the response to statin. Our results suggest that manipulation of the gut microbiota composition can be an interesting and effective treatment strategy to blood lipid control among CAD patients.

Combined Lowering Effects of Rosuvastatin and L. acidophilus on Cholesterol Levels in Rat.

Statins are a class of lipid-lowering drugs commonly used in the prevention of cardiovascular diseases. However, statin therapy presents many limitations, which have led to an increased interest in non-drug therapies, such as probiotics, to improve blood cholesterol levels. Indeed, probiotic strains such as Lactobacillus acidophilus have been found to improve blood lipid profiles, especially in reducing total cholesterol and LDL-C levels. In this study, we established a high-cholesterol rat model and studied the effect of Lactobacillus acidophilus administration alone or in conjunction with rosuvastatin. We were able to show that indeed Lactobacillus exerts a cholesterol-lowering effect. Additionally, we observed that when administered together, rosuvastin and Lactobacillus exert a combined cholesterol-lowering effect. Altogether, our data advocate for the possibility of establishing probiotics as non-drug supplements for the treatment of hypercholesterolemia.