Journal of Cardiovascular Translational Research

Postoperative atrial fibrillation (POAF) is a frequent complication associated with increased periprocedural mortality and morbidity after cardiac surgery. Our study aimed to identify the difference in exosomal miRNA and further explore its role in the diagnosis of POAF. First, the differentially expressed miRNAs (DEMs) were obtained by high-throughput RNA sequencing. Second, the DEMs target genes were put into gene ontology (GO) and KEGG pathway analysis. Third, real-time quantification PCR (RT-qPCR) was used to verify the DEMs. Finally, we revealed 23 DEMs in POAF patients. Furthermore, analysis of gene function revealed that DEMs may affect atrial structure through many signaling pathways. We also found that miR-122-5p was up-regulated in POAF patients, but there are no significant changes in miR-191-5p, miR-181a-5p, miR-155-5p and miR-151a-5p. Our study revealed that exosomal miRNAs exert enormous potential in evaluating the severity or prognostic of POAF.

Ischemic heart disease (IHD) or myocardial ischemia is one of the leading causes of mortality all over the world. There is a definite need for new approaches to improve therapies and diagnostics. The pathological process leading to IHD is associated with an altered expression of genes that are important for cardiac functions. MicroRNAs (miRNAs) have emerged as one of the central players regulating gene expression via degradation or translational inhibition of their target genes. Increasing evidence indicates that miRNAs may serve as potential diagnostic biomarkers and innovative therapeutic targets in several human diseases including cardiovascular disease. Here, we review the latest advances in the identification and validation of myocardial ischemia-related miRNAs and their target genes and discuss the roles of specific miRNAs in regulating ischemia-related cardiac injury, including apoptosis, fibrosis, arrhythmia, and angiogenesis.

The beneficial effects of physical activity on the cardiovascular system nowadays have achieved the relevance of clinical evidence. In fact, several studies have documented the benefits of exercise training in the prevention of the cardiovascular risk. Abnormalities of insulin signaling transduction account for the impairment of insulin sensitivity and development of insulin resistance, which, in turn, is responsible for the enhancement of cardiovascular risk. Insulin sensitivity is related to the degree of physical activity, and physical training has been shown to ameliorate insulin action in insulin-resistant subjects. This effect is mediated by the improvement of the molecular abnormalities that are responsible of the insulin resistance, contributing in this way to restore the physiological insulin sensitivity. However, it should be underlined that mechanisms that account for this phenomenon are extremely complex and still unclear. Further studies are required to better clarify the molecular basis of the exercise-evoked improvement of insulin signal.

Large artery stiffness, as measured by pulse wave velocity, is correlated with high blood pressure and may be a causative factor in essential hypertension. The extracellular matrix components, specifically the mix of elastin and collagen in the vessel wall, determine the passive mechanical properties of the large arteries. Elastin is organized into elastic fibers in the wall during arterial development in a complex process that requires spatial and temporal coordination of numerous proteins. The elastic fibers last the lifetime of the organism but are subject to proteolytic degradation and chemical alterations that change their mechanical properties. This review discusses how alterations in the amount, assembly, organization, or chemical properties of the elastic fibers affect arterial stiffness and blood pressure. Strategies for encouraging or reversing alterations to the elastic fibers are addressed. Methods for determining the efficacy of these strategies, by measuring elastin amounts and arterial stiffness, are summarized. Therapies that have a direct effect on arterial stiffness through alterations to the elastic fibers in the wall may be an effective treatment for essential hypertension.

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remedē System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea–hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea–hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea–hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden.

Left atrial sphericity index (LASI) is one significant geometric remodeling parameter to evaluate the prognosis of atrial fibrillation (AF). We aimed to determine whether transthoracic echocardiography (TTE)–derived LASI may help predict the outcomes following AF radiofrequency catheter ablation (RFCA). This prospective study enrolled 190 consecutive AF patients who underwent TTE 24 h before RFCA. LASI was calculated as the ratio of left atrial maximum volume to spherical volume. After 1-year follow-up, 56 patients (29.5%) relapsed. Multivariate Cox regression showed that LASI (hazard ratio = 1.48, 95% Cl 1.15–1.92, P = 0.003) was an independent predictor of AF recurrence. Stratifying patients into four subgroups with different LAVI showed that high LASI value indicated a high risk of recurrence, especially in patients with mildly and moderately enlarged atria (the recurrence rate was 0% vs. 26.3%, P = 0.049; 9.5% vs. 40.9%, P = 0.018, respectively). In conclusion, TTE-derived LASI may be useful to predict AF recurrence after RFCA.

The DNA sequencing technology developed by Frederick Sanger in the 1970s established genomics as the basis of comparative genetics. The recent invention of next-generation sequencing (NGS) platform has added a new dimension to genome research by generating ultra-fast and high-throughput sequencing data in an unprecedented manner. The advent of NGS technology also provides the opportunity to study genetic diseases where sequence variants or mutations are sought to establish a causal relationship with disease phenotypes. However, it is not a trivial task to seek genetic variants responsible for genetic diseases and even harder for complex diseases such as diabetes and cancers. In such polygenic diseases, multiple genes and alleles, which can exist in healthy individuals, come together to contribute to common disease phenotypes in a complex manner. Hence, it is desirable to have an approach that integrates omics data with both knowledge of protein structure and function and an understanding of networks/pathways, i.e. functional genomics and systems biology; in this way, genotype–phenotype relationships can be better understood. In this review, we bring this ‘bottom-up’ approach alongside the current NGS-driven genetic study of genetic variations and disease aetiology. We describe experimental and computational techniques for assessing genetic variants and their deleterious effects on protein structure and function.

The current work was developed to explore the functions and possible mechanism of PRG4 in cardiac hypertrophy and heart failure. Ang II-stimulated H9c2 cells and AC16 cells were used as in vitro cell models. The binding relation between genes in cells was explored using luciferase reporter assays and RNA immunoprecipitation assay. The cardiac functions of rats received transverse-ascending aortic constriction (TAC) surgery and adeno-associated virus (AAV) injection were examined with echocardiography. The myocardial histological changes were observed using H&E, wheat germ agglutinin, and sirius red staining. It was discovered that PRG4 silencing attenuated cell hypertrophy and fibrosis and inactivated the Smad pathway under Ang II treatment. PRG4 was targeted by miR-758-3p, and miR-758-3p interacted with long noncoding RNA DANCR. DANCR silencing inhibited cardiac dysfunction, fibrosis, and TGFβ1/Smad pathway. In addition, DANCR was highly expressed in myocardial extracellular vesicles. Overall, DANCR depletion prevents heart failure by inhibiting cardiac hypertrophy and fibrosis via the miR-758-3p/PRG4/Smad pathway.

Non-invasive imaging has become fundamental in translating findings from basic science research into clinical applications. In this aspect, positron-emission tomography (PET) offers important advantages over other common imaging modalities like single-photon emission computed tomography, computed tomography, and magnetic resonance imaging (MRI), since PET provides superior detection sensitivity in the evaluation of different cardiovascular targets and pathways at the cellular and subcellular level, and because it is a well-established technique for absolute image quantification. The development and the introduction of dedicated small animal PET systems have greatly facilitated and contributed to advancements in the translation of novel radio-labeled compounds from experimental to clinical practice. The scope of the present article is to review the most relevant and successful PET applications in cardiovascular translational research.