Shengguang Ding

miR-19b attenuates H2O2-induced apoptosis in rat H9C2 cardiomyocytes via targeting PTEN

Myocardial ischemia-reperfusion (I-R) injury lacks effective treatments. The miR-17-92 cluster plays important roles in regulating proliferation, apoptosis, cell cycle and other pivotal processes. However, their roles in myocardial I-R injury are largely unknown. In this study, we found that miR-19b was the only member of the miR-17-92 cluster that was downregulated in infarct area of heart samples from a murine model of I-R injury. Meanwhile, downregulation of miR-19b was also detected in H2O2-treated H9C2 cells in vitro mimicking oxidative stress occurring during myocardial I-R injury. Using flow cytometry and Western blot analysis, we found that overexpression of miR-19b decreased H2O2-induced apoptosis and improved cell survival, while downregulation of that had inverse effects. Furthermore, PTEN was negatively regulated by miR-19b at the protein level while silencing PTEN could completely block the aggravated impact of miR-19b inhibitor on H2O2-induced apoptosis in H9C2 cardiomyocytes, indicating PTEN as a downstream target of miR-19b controlling H2O2-induced apoptosis. These data indicate that miR-19b overexpression might be a novel therapy for myocardial I-R injury.

MiR-222 in Cardiovascular Diseases: Physiology and Pathology

MicroRNAs (miRNAs and miRs) are endogenous 19–22 nucleotide, small noncoding RNAs with highly conservative and tissue specific expression. They can negatively modulate target gene expressions through decreasing transcription or posttranscriptional inducing mRNA decay. Increasing evidence suggests that deregulated miRNAs play an important role in the genesis of cardiovascular diseases. Additionally, circulating miRNAs can be biomarkers for cardiovascular diseases. MiR-222 has been reported to play important roles in a variety of physiological and pathological processes in the heart. Here we reviewed the recent studies about the roles of miR-222 in cardiovascular diseases. MiR-222 may be a potential cardiovascular biomarker and a new therapeutic target in cardiovascular diseases.

miR-19b controls cardiac fibroblast proliferation and migration

Cardiac fibrosis is a fundamental constituent of a variety of cardiac dysfunction, making it a leading cause of death worldwide. However, no effective treatment for cardiac fibrosis is available. Therefore, novel therapeutics for cardiac fibrosis are highly needed. Recently, miR‐19b has been found to be able to protect hydrogen peroxide (H2O2)‐induced apoptosis and improve cell survival in H9C2 cardiomyocytes, while down‐regulation of miR‐19b had opposite effects, indicating that increasing miR‐19b may be a new therapeutic strategy for attenuating cellular apoptosis during myocardial ischaemia–reperfusion injury. However, considering the fact that microRNAs might exert a cell‐specific role, it is highly interesting to determine the role of miR‐19b in cardiac fibroblasts. Here, we found that miR‐19b was able to promote cardiac fibroblast proliferation and migration. However, miR‐19b mimics and inhibitors did not modulate the expression level of collagen I. Pten was identified as a target gene of miR‐19b, which was responsible for the effect of miR‐19b in controlling cardiac fibroblast proliferation and migration. Our data suggest that the role of miR‐19b is cell specific, and systemic miR‐19b targeting in cardiac remodelling might be problematic. Therefore, it is highly needed and also urgent to investigate the role of miR‐19b in cardiac remodelling in vivo.

Serum-Derived Extracellular Vesicles Protect Against Acute Myocardial Infarction by Regulating miR-21/PDCD4 Signaling Pathway

Acute myocardial infarction (AMI) represents a leading cause of morbidity and mortality worldwide. Extracellular vesicles (EVs) are being recognized as a promising therapeutic approach in protecting against MI. Serum is a rich source of EVs, which transports various microRNAs (miRNAs, miRs). EVs from serum have been shown beneficial for protecting against ischemia-reperfusion injury; however, their roles in AMI are unclear. In addition, whether a miRNA might be responsible for the effects of serum EVs on protecting against AMI is undetermined. Here, we demonstrated that serum EVs significantly reduced cardiomyocytes apoptosis in both cellular and mouse models of AMI, and dramatically attenuated the infarct size in mouse hearts after AMI. Inhibition of miR-21 was shown to reduce the protective effects of serum EVs in inhibiting cardiomyocytes apoptosis. miR-21 was decreased in mouse hearts after AMI, while serum EVs increased that. In addition, the programmed cell death 4 (PDCD4) expression was identified as a target gene of miR-21. Therefore, our study showed the protective effects of serum EVs on AMI, and provided a novel strategy for AMI therapy.

Circular RNAs in Vascular Functions and Diseases

Vascular disease is one of the top five causes of death and affects a variety of other diseases, such as heart, nervous system, and metabolic disorders. Vascular dysfunction is a hallmark of ischemia, cancer, and inflammatory diseases and can accelerate the progression of diseases. Circular RNAs (circRNAs) are a new type of noncoding RNAs with covalent bond ring structure, which have been reported to be abnormally expressed in many human diseases. circRNAs regulate gene expression through the sponging of microRNAs (miRNAs) and can also be used as disease biomarkers. Here we will summarize the functions of circRNAs in vascular diseases, including vascular dysfunction, atherosclerosis, diabetes mellitus-related retinal vascular dysfunction, chronic thromboembolic pulmonary hypertension, carotid atherosclerotic disease, hepatic vascular invasion in hepatocellular carcinoma, aortic aneurysm, coronary artery disease, and type 2 diabetes mellitus.

Therapeutic Effects of Ischemic-Preconditioned Exosomes in Cardiovascular Diseases

Despite years of researches, cardiovascular disease (CVD) remains the most common cause of death around the world. Lots of studies showed that by pretreating with short nonfatal ischemia in in situ organ or distant organ, one could develop tolerance to the following fatal ischemia. The process is called ischemic preconditioning (IPC). IPC prepare the heart for damage by producing inflammatory signals, miRNA, neuro system stimulation and exosomes. Among them, exosomes have been gaining increasing interest since it is characterized by its capability to carry information and its specific ligand-receptor system. Here we will discuss IPC induced exosomes and its protective effects during ischemic heart disease.

C/EBPB-CITED4 in Exercised Heart

C/EBPB is a crucial transcription factor, participating in a variety of biological processes including cell proliferation, differentiation and development. In the cardiovascular system, C/EBPB-CITED4 signaling is known as a signaling pathway mediating exercise-induced cardiac growth. After its exact role in exercised heart firstly reported in 2010, more and more evidence confirmed that. MicroRNA (e.g. miR-222) and many molecules (e.g. Alpha-lipoic acid) can regulate this pathway and then involve in the cardiac protection effect induced by endurance exercise training. In addition, in cardiac growth during pregnancy, C/EBPB is also a required regulator. This chapter will give an introduction of the C/EBPB-CITED4 signaling and the regulatory network based on this signaling pathway in exercised heart.