Subcellular mass spectrometric detection unveils hyperglycemic memory in the diabetic heart.

Background: Intensive glycemic control is insufficient to reduce the risk of heart failure in patients with diabetes mellitus. While the hyperglycemic memory in the diabetic cardiomyopathy has been well documented, its underlying mechanisms are not fully understood. The present study tried to investigate whether the dysregulated proteins/biological pathways, which persistently altered in diabetic hearts during normoglycemia, participate in the hyperglycemic memory.

Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy.

CFIRL is a long noncoding RNA (lncRNA), we previously identified as the most significantly upregulated lncRNA in the failing hearts of patients with dilated cardiomyopathy (DCM). In this study, we determined the function of CFIRL and its role in DCM. Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts.

Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts.

Heart failure (HF) is manifested by transcriptional and posttranscriptional reprogramming of critical genes. Multiple studies have revealed that microRNAs could translocate into subcellular organelles such as the nucleus to modify gene expression. However, the functional property of subcellular Argonaute2 (AGO2), the core member of the microRNA machinery, has remained elusive in HF.

AGO2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation.

Background: Diabetes is associated with cardiovascular complications. microRNAs translocate into subcellular organelles to modify genes involved in diabetic cardiomyopathy. However, functional properties of subcellular AGO2 (Argonaute2), a core member of miRNA machinery, remain elusive.

LncRNA ZNF593-AS alleviates diabetic cardiomyopathy via suppressing IRF3 signaling pathway.

Diabetes could directly induce cardiac injury, leading to cardiomyopathy. However, treatment strategies for diabetic cardiomyopathy remain limited. ZNF593-AS knockout and cardiomyocyte-specific transgenic mice were constructed.

Positive feedback loop of miR-320 and CD36 regulates the hyperglycemic memory-induced diabetic diastolic cardiac dysfunction.

Intensive glycemic control is insufficient for reducing the risk of heart failure among patients with diabetes mellitus (DM). While the "hyperglycemic memory" phenomenon is well documented, little is known about its underlying mechanisms. In this study, a type 1 DM model was established in C57BL/6 mice using streptozotocin (STZ).

MicroRNAs in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide, despite the wide diversity of molecular targets identified and the development of therapeutic methods. MicroRNAs (miRNAs) are a class of small (about 22 nucleotides) non-coding RNAs (ncRNAs) that negatively regulate gene expression at the post-transcriptional level in the cytoplasm and play complicated roles in different CVDs. While miRNA overexpression in one type of cell protects against heart disease, it promotes cardiac dysfunction in another type of cardiac cell.

Overexpression of cytosolic long noncoding RNA cytb protects against pressure-overload-induced heart failure via sponging microRNA-103-3p.

Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. To date, only limited studies have reported the role of mitochondria-derived lncRNAs in heart failure (HF). In the current study, recombinant adeno-associated virus 9 was used to manipulate lncRNA cytb (lnccytb) expression .

Hyperglycemic memory in diabetic cardiomyopathy.

Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes.

The double face of miR-320: cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction.

MicroRNAs (miRNAs) are aberrantly expressed in the pathophysiologic process of heart failure (HF). However, the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported, which might be covered by the globe effects of it on the heart. In the current study, Langendorff system was applied to isolate cardiomyocytes (CMs) and cardiac fibroblasts (CFs) from transverse aortic constriction (TAC)-induced mice.

LncRNA ZNF593-AS Alleviates Contractile Dysfunction in Dilated Cardiomyopathy.

[Figure: see text].

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. Multiple metabolic disorders, such as hyperlipidemia, hyperglycemia, insulin resistance and obesity, have been reportedly associated with NAFLD, but little is known about the detailed mechanisms.

Methods And Results: Here, we explored the effects of multiple metabolic disorders, especially hyperglycemia on lipid accumulation in liver using several well-established animal models.

Identification of ncRNA-Mediated Functions of Nucleus-Localized miR-320 in Cardiomyocytes.

In recent years, systematic analyses of the subcellular distribution of microRNAs (miRNAs) suggest that the majority of miRNAs are present in both nuclear and cytoplasmic compartments. However, the full extent of nuclear miRNA function in cardiomyocytes is currently unknown. Here, subcellular fractionation, followed by the miRNA microarray, revealed that most miRNAs were detectable in both nuclear and cytoplasmic fractions of cardiomyocytes.

Nuclear miR-665 aggravates heart failure via suppressing phosphatase and tensin homolog transcription.

Although numerous miRNAs have been discovered, their functions in the different subcellular organelles have remained obscure. In this study, we found that miR-665 was enriched in the nucleus of cardiomyocytes, and then investigated the underlying role of nuclear miR-665 in heart failure. RNA fluorescence in situ hybridization assays in human heart tissue sections and primary cardiomyocytes showed that miR-665 was localized in the nucleus of cardiomyocytes.

Nuclear miR-320 Mediates Diabetes-Induced Cardiac Dysfunction by Activating Transcription of Fatty Acid Metabolic Genes to Cause Lipotoxicity in the Heart.

Rationale: Diabetes mellitus is often associated with cardiovascular complications, which is the leading cause of morbidity and mortality among patients with diabetes mellitus, but little is known about the mechanism that connects diabetes mellitus to the development of cardiovascular dysfunction.

Objective: We aim to elucidate the mechanism underlying hyperglycemia-induced cardiac dysfunction on a well-established db/db mouse model for diabetes mellitus and diabetic complications that lead to heart failure.

Methods And Results: We first profiled the expression of microRNAs (miRNAs) by microarray and quantitative reverse transcription polymerase chain reaction on db/db mice and identified miR-320 as a key miRNA associated with the disease phenotype.