Hualin Yan

Bio: Hualin Yan is an academic researcher from Sichuan University. The author has contributed to research in topics: Cardiac function curve & Likelihood ratios in diagnostic testing. The author has an hindex of 4, co-authored 12 publications receiving 93 citations. Previous affiliations of Hualin Yan include Boston Children's Hospital.

Contrary microRNA Expression Pattern Between Fetal and Adult Cardiac Remodeling: Therapeutic Value for Heart Failure

Abstract: microRNAs (miRNAs) belong to a class of non-coding RNAs that regulate post-transcriptional gene expression during development and disease. Growing evidence indicates abundant miRNA expression changes and their important role in cardiac hypertrophy and failure. However, the role of miRNAs in fetal cardiac remodeling is little known. Here, we investigated the altered expression of fifteen miRNAs in rat fetal cardiac remodeling compared with adult cardiac remodeling. Among fifteen tested miRNAs, eleven and five miRNAs (miR-199a-5p, miR-214-3p, miR-155-3p, miR-155-5p and miR-499-5p) are significantly differentially expressed in fetal and adult cardiac remodeling, respectively. After comparison of miRNA expression in fetal and adult cardiac remodeling, we find that miRNA expression returns to the fetal level in adult cardiac failure and is activated in advance of the adult level in fetal failure. The current study highlights the contrary expression pattern between fetal and adult cardiac remodeling and that supports a novel potential therapeutic approach to treating heart failure.

Adeno-associated virus-mediated delivery of anti-miR-199a tough decoys attenuates cardiac hypertrophy by targeting PGC-1alpha

Abstract: MicroRNAs (miRNAs) are important regulators in the process of cardiac hypertrophy and heart failure. Previous studies have shown that miR-199a is upregulated in pressure-overload cardiac hypertrophy and that inhibition of miR-199a attenuates cardiac hypertrophy in vitro. However, the therapeutic role of anti-miR-199a treatment in the cardiac hypertrophy in vivo model is less known. Here, we show an efficient and useful method to treat mouse cardiac hypertrophy and restore cardiac function through injection of adeno-associated virus (AAV)-mediated anti-miR-199a tough decoys (TuDs). RNA-seq transcriptome analysis indicated that genes related to cytoplasmic translation and mitochondrial respiratory chain complex assembly were upregulated in anti-miR-199a-treated recovered hearts. We further validated that PGC-1α is the direct target of miR-199a involved in the therapeutic effect and the regulation of the PGC-1α/ERRα axis and that the downstream pathway of mitochondrial fatty acid oxidation and oxidative phosphorylation constitute the underlying mechanism of the restored mitochondrial structure and function in our anti-miR-199a-treated mice. Our study highlights the important regulatory role of miR-199a in cardiac hypertrophy and the value of the AAV-mediated miRNA delivery system.

Carotid Intraplaque Neovascularization on Contrast-Enhanced Ultrasound Correlates with Cardiovascular Events and Poor Prognosis: A Systematic Review and Meta-analysis.

Abstract: The goal of this meta-analysis is to investigate whether carotid intraplaque neovascularization (IPN) on contrast-enhanced ultrasound (CEUS) correlates with past cardiovascular events (CVEs) and prognosis. The present meta-analysis included 22 studies involving 3232 patients. The pooled analysis revealed that the presence of IPN was significantly associated with a higher incidence of future CVEs (pooled relative risk = 3.28, 95% confidence interval [CI]: 2.28–4.73) and a lower event-free probability (pooled hazard ratio = 2.51, 95% CI: 1.48–4.27). The presence of IPN was significantly associated with higher rates of past cardiac events (odds ratio = 4.25, 95% CI: 2.48–7.29) and past cerebrovascular accidents (odds ratio = 4.83, 95% CI: 2.66–8.78). Our results suggest that carotid IPN on CEUS significantly correlates with past cardiac events and cerebrovascular accidents and can predict future CVEs. Carotid CEUS is useful in CVE risk stratification.

Cellular and molecular pathobiology of heart failure with preserved ejection fraction.

Abstract: Heart failure with preserved ejection fraction (HFpEF) affects half of all patients with heart failure worldwide, is increasing in prevalence, confers substantial morbidity and mortality, and has very few effective treatments. HFpEF is arguably the greatest unmet medical need in cardiovascular disease. Although HFpEF was initially considered to be a haemodynamic disorder characterized by hypertension, cardiac hypertrophy and diastolic dysfunction, the pandemics of obesity and diabetes mellitus have modified the HFpEF syndrome, which is now recognized to be a multisystem disorder involving the heart, lungs, kidneys, skeletal muscle, adipose tissue, vascular system, and immune and inflammatory signalling. This multiorgan involvement makes HFpEF difficult to model in experimental animals because the condition is not simply cardiac hypertrophy and hypertension with abnormal myocardial relaxation. However, new animal models involving both haemodynamic and metabolic disease, and increasing efforts to examine human pathophysiology, are revealing new signalling pathways and potential therapeutic targets. In this Review, we discuss the cellular and molecular pathobiology of HFpEF, with the major focus being on mechanisms relevant to the heart, because most research has focused on this organ. We also highlight the involvement of other important organ systems, including the lungs, kidneys and skeletal muscle, efforts to characterize patients with the use of systemic biomarkers, and ongoing therapeutic efforts. Our objective is to provide a roadmap of the signalling pathways and mechanisms of HFpEF that are being characterized and which might lead to more patient-specific therapies and improved clinical outcomes.

The roles of microRNAs in spinal cord injury.

Abstract: Background and purpose: Spinal cord injury (SCI) involves serious damage that can result in abnormal or absent motor and sensory functions and a disruption of autonomic function, and a series of pathological reactions occur after the injury. As a type of small non-coding RNA, microRNAs (miRNAs) have been verified to inhibit gene expression via post-transcriptional regulation. This review mainly focuses on recent advances regarding the roles of miRNAs following SCI. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. The studies regarding the roles of miRNAs following SCI were identified through PubMed, Embase and Web of Science. We summarise the changes in expression levels of miRNAs and discuss the roles of miRNAs after SCI. Results: A total of 77 empirical studies meeting the inclusion criteria were identified. Existing studies showed that miRNAs were temporally altered and had effects on apoptosis, inflammation, angiogenesis, astrogliosis, ol...

Biomarkers in Routine Heart Failure Clinical Care.

Abstract: Heart failure is a clinical condition with complex pathophysiology that involves many different processes. Diagnosis is often difficult in patients presenting for the first time with breathlessness. Many biomarkers have been identified that are elevated in heart failure and their role in assessing prognosis has also been investigated. However, at present the natriuretic peptides appear to be the gold standard biomarker against which the other biomarkers are compared. In this review we will examine the evidence behind the other biomarkers for use in heart failure patients and the current guidelines for their use.

Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression

Abstract: Heart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. We generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression. Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort. The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content ≥ 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rank p value < 1.0 × 10− 4]. Our results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.

Functional requirement of Dicer1 and miR-17-5p in reactive astrocyte proliferation after spinal cord injury in the mouse.

Abstract: Reactive astrogliosis after spinal cord injury (SCI) contributes to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte proliferation upon injury remain partially understood. MicroRNAs (miRNAs) function as a major class of post-transcriptional gene expression regulators that participate in many biological processes. However, miRNA function during reactive astrogliosis, particularly in injury-induced astrocyte proliferation, has not been carefully examined. In this study, we conditionally deleted Dicer1 gene encoding an enzyme that is required for mature miRNA generation, and examined the proliferative behavior of Dicer1-null reactive astrocytes in the transected mouse spinal cord. We found that injury-induced proliferation is blocked in Dicer1-null astrocytes. Previous reports indicate that miR-17-5p family members are upregulated during SCI. We therefore tested functional contribution of miR-17-5p to the proliferation of reactive astrocytes in vitro. Our results showed that a synthetic miR-17-5p mimic is able to rescue the proliferation defect of Dicer1-null astrocytes, while an antisense inhibitor of miR-17-5p blocked lipopolysaccharide-induced astrocytic proliferation. Similar results are also observed in leukemia inhibitory factor (LIF)-treated astroglial cultures suggesting that miR-17-5p particularly modulates reactive astrocyte proliferation initiated by LIF presumably via the JAK/STAT3 pathway. Furthermore, overexpression of miR-17-5p leads to decrease of several cell cycle regulators in cultured astroglia and astrocytoma cell line C6. Our conclusion is that miRNAs are indispensable to the injury-induced reactive astrocyte proliferation, and that miR-17-5p may be a major player regulating this pathological process by affecting cell cycle machinery.