CircRNA-mediated pathology: a new preliminary insight into the mechanism of type II cardio-renal syndrome.

AIM: The aim of this research was to investigate the expression of peripheral blood circular RNA (circRNA) in patients with type II cardio-renal syndrome, uncover the potential function and possible mechanisms mediated by circRNAs, and ultimately provide gene target support for the treatment of type II cardio-renal syndrome. METHODS: CircRNAs in the peripheral blood from five healthy individuals and 20 type II cardio-renal syndrome patients were collected for micro-array analysis. Another cohort study consisting of 12 normal cases and 15 type II cardiorenal syndrome patients was conducted to verify the chosen circRNA by quantitative real-time polymerase chain reaction. RESULTS: A total of 2 884 circRNAs were found to be differentially expressed in the group of patients with type II cardio-renal syndrome. Of these, 1 989 were upregulated and 895 were downregulated. One circRNA was then selected as a candidate biomarker and further validated in the second cohort. CONCLUSIONS: Differentially expressed mRNAs between patients with type II cardio-renal syndrome and healthy controls were enriched in two pathways, including haematopoietic cell lineage and cell adhesion molecules. CircRNA-mediated pathology is indispensable and plays an important role in the progress of type II cardio-renal syndrome. More importantly, hsa_cir_0001763 may be an important character in circRNA-mediated pathology.

The Role of Myocardial Mitochondrial Quality Control in Heart Failure.

At present, the treatment of heart failure has entered the plateau phase, and it is necessary to thoroughly study the pathogenesis of heart failure and find out the corresponding treatment methods. Myocardial mitochondria is the main site of cardiac energy metabolism, whose dysfunction is an important factor leading to cardiac dysfunction and heart failure. Mitochondria are highly dynamic organelles. Continuous biogenesis, fusion, fission and mitophagy, contribute to the balance of mitochondria's morphology, quantity, and quality, which is called mitochondrial quality control. Mitochondrial quality control is the cornerstone of normal mitochondrial function and is found to play an important role in the pathological process of heart failure. Here, we provide an overview of the mechanisms of mitochondrial quality control and recent studies on mitochondrial quality control in heart failure, hoping to provide new ideas for drug development in heart failure.

Xin Fu Kang oral liquid inhibits excessive myocardial mitophagy in a rat model of advanced heart failure.

Heart failure caused by myocardial infarction is a common cardiovascular disease with high mortality rate. Myocardial mitophagy is involved in the process of occurrence and development of heart failure. In this study, we aimed to investigate the effects of Xin Fu Kang (XFK) oral liquid on myocardial mitophagy in a rat model of advanced heart failure. The rat model of advanced heart failure was established by ligating the left anterior descending (LAD) artery for eight weeks. Captopril and XFK were given by gavage separately. Cardiac function and myocardial mitochondrial ultrastructure were observed. Co-localization of mitophagy-related proteins was observed by fluorescence microscopy. Quantitative polymerase chain reaction (qPCR) and western blotting were performed for mRNA and protein level detection, respectively. Compared with the sham group, advanced heart failure group showed a significant reduction in cardiac function with destruction of myocardial mitochondrial structure. Co-localization between mitophagy-related proteins (parkin, p62, and LC3) and mitochondria increased significantly. The mRNA and protein levels of pink1, parkin, p62, and LC3 indicated that excessive mitophagy was observed in the rat model of advanced heart failure. XFK intervention could regulate pink/parkin pathway and inhibit excessive mitophagy.

Deficiency of interfibrillar mitochondria in post-acute myocardial infarction heart failure.

Mitochondrial dysfunction plays an important role in the progress of heart failure (HF). A pronounced variability of defects in mitochondrial subpopulations is reported to occur in various disease models. The aim of the study was to define the defects in the ultra structure and bioenergetic function of cardiac mitochondria in acute myocardial infarction-induced HF. AMI-induced HF rats were treated with saline (4.0ml/kg) for 8weeks. The ultra structure of myocardial mitochondrial subpopulations was assessed by electron microscope. The bioenergetic function of myocardial mitochondrial subpopulations was evaluated through Clark oxygen electrode. Results indicated that myocardial mitochondrial subpopulations in Model group had abnormal mitochondrial morphology which manifested as swelling and vacuoles, membrane lysis, fuzzy ridge structure, cristae lysis or disappear in IFM particularly, while SSM was almost survived in AMI induced heart failure. Results showed that the oxidative phosphorylation function of respiratory chain of NADH oxidation was impaired notably. Compared with Sham group, both P/O (P<0.01) and OPR (P<0.01) of myocardial IFM in model rats decreased, and V3 (P<0.01), P/O (P<0.05) and OPR (P<0.01) of SSM in Model group decreased either. Meanwhile, the oxidative phosphorylation function of respiratory chain of FADH oxidation was injured in SSM particularly, which presented as the decreased P/O (P<0.01). We propose that the mitochondrial defect of severe HF mostly lies in the interfibrillar mitochondria rather than in the subsarcolemmal mitochondria.

The relationship between neutrophil to lymphocyte ratio and artery stiffness in subtypes of hypertension.

Recently, neutrophil/lymphocyte ratio (NLR) has been proved to be a useful indicator of inflammation and cardiovascular risk. Brachial-ankle pulse wave velocity is an indicator for early atherosclerotic changes. It is unknown whether NLR differs in subtypes of hypertension, and little research has been performed on the relationship between NLR and arteriosclerosis in subtypes of hypertension. The purpose of this article was to investigate their relationship. A total of 217 consecutive patients with hypertension and 132 persons without hypertension were included. All hypertension patients were divided into three groups according to office blood pressure. Brachial-ankle pulse wave velocity was elevated in patients with isolated systolic hypertension, isolated diastolic hypertension, and systolic and diastolic hypertension compared with normotensive controls. NLR in patients with isolated systolic hypertension and systolic and diastolic hypertension were higher than in normotensive controls. Correlation analysis revealed a positive correlation between NLR and brachial-ankle pulse wave velocity. Multivariate linear regression analysis showed that NLR was an effective indicator for brachial-ankle pulse wave velocity.

[Endoplasmic reticulum stress and vascular endothelial cell apoptosis].

Endoplasmic reticulum stress (ERS) is a new pathway of apoptosis following the discovery of death receptor signaling pathway and mitochondrial pathway. By activating the unfolded protein response (UPR), ERS can suspend protein synthesis, restore the endoplasmic reticulum homeostasis, and thus play a protective role for cells; however, if the inducing factors of ERS persist, ERS will continue to trigger C/EBP homologous protein, JNK, caspase, or other pathways to induce apoptosis. In addition, the injury and apoptosis of vascular endothelial cells are key links in various diseases and pathophysiologic processes, and research has also shown that vascular endothelial cell apoptosis is closely related with the ERS. Effective intervention of ERS may restrain apoptosis and protect the vascular endothelium. This article reviews the recent research advances in ERS and its role in vascular endothelial cell apoptosis.