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Background: Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classic epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in patients with hypertension is important for investigating hypertension mechanisms. Methods: Differential genomic DNA methylation in patients with hypertension, individuals with prehypertension, and healthy control individuals was screened using Illumina 450K BeadChip and verified by pyrosequencing. Plasma OVGP1 (oviduct glycoprotein 1) levels were determined using an enzyme-linked immunosorbent assay. Ovgp1 transgenic and knockout mice were generated to analyze the function of OVGP1. The blood pressure levels of the mouse models were measured using the tail-cuff system and radiotelemetry methods. The role of OVGP1 in vascular remodeling was determined by vascular relaxation studies. Protein–protein interactions were investigated using a pull-down/mass spectrometry assay and verified with coimmunoprecipitation and pull-down assays. Results: We found a hypomethylated site at cg20823859 in the promoter region of OVGP1 and plasma OVGP1 levels were significantly increased in patients with hypertension. This finding indicates that OVGP1 is associated with hypertension. In Ovgp1 transgenic mice, OVGP1 overexpression caused an increase in blood pressure, dysfunctional vasoconstriction and vasodilation, remodeling of arterial walls, and increased vascular superoxide stress and inflammation, and these phenomena were exacerbated by angiotensin II infusion. In contrast, OVGP1 deficiency attenuated angiotensin II–induced vascular oxidase stress, inflammation, and collagen deposition. These findings indicate that OVGP1 is a prohypertensive factor that directly promotes vascular remodeling. Pull-down and coimmunoprecipitation assays showed that MYH9 (nonmuscle myosin heavy chain IIA) interacted with OVGP1, whereas inhibition of MYH9 attenuated OVGP1-induced hypertension and vascular remodeling. Conclusions: Hypomethylation at cg20823859 in the promoter region of OVGP1 is associated with hypertension and induces upregulation of OVGP1. The interaction between OVGP1 and MYH9 contributes to vascular remodeling and dysfunction. Therefore, OVGP1 is a prohypertensive factor that promotes vascular remodeling by binding with MYH9.

Aim: To investigate the expression profiles of circRNAs after intracerebral hemorrhage (ICH). Materials & methods: RNA sequencing and qRT-PCR were used to investigate and validate circRNA expression levels. Bioinformatics analysis was performed to explore potential functions of the circRNAs. Results: Expression levels of 15 circRNAs were consistently altered in patients with ICH compared with their expression levels in hypertension. Three circRNAs, hsa_circ_0001240, hsa_circ_0001947 and hsa_circ_0001386, individually or combined, were confirmed as promising biomarkers for predicting and diagnosing ICH. The circRNAs were involved mainly in lysine degradation and the immune system. Conclusion: This is the first study to report expression profiles of circRNAs after ICH and to propose that three circRNAs are potential biomarkers for ICH.

Rationale: The progressive disruption of extracellular matrix (ECM) proteins, particularly early elastin fragmentation followed by abnormalities in collagen fibril organization, are key pathological processes that contribute to dissecting abdominal aortic aneurysm (AAA) pathogenesis. Lysyl hydroxylase 1 (LH1) is essential for type I/III collagen intermolecular crosslinking and stabilization. However, its function in dissecting AAA has not been explored. Here, we investigated whether LH1 is significantly implicated in dissecting AAA progression and therapeutic intervention. Methods and Results: Sixteen-week-old male LH1-deficient and wild-type (WT) mice on the C57Bl/6NCrl background were infused with angiotensin II (Ang II, 1000 ng/kg per minute) via subcutaneously implanted osmotic pumps for 4 weeks. Ang II increased LH1 levels in the abdominal aortas of WT mice, whereas mice lacking LH1 developed dissecting AAA. To evaluate the related mechanism, we performed whole-transcriptomic analysis, which demonstrated that LH1 deficiency aggravated gene transcription alterations; in particular, the expression of thrombospondin-1 was markedly upregulated in the aortas of LH1-deficient mice. Furthermore, targeting thrombospondin-1 with TAX2 strongly inhibited the proinflammatory process, matrix metalloproteinase (MMP) activity and vascular smooth muscle cells (VSMCs) apoptosis, ultimately decreasing the incidence of dissecting AAA. Restoration of LH1 protein expression in LH1-deficient mice by intraperitoneal injection of an adeno-associated virus normalized thrombospondin-1 levels, subsequently alleviating dissecting AAA formation and preserving aortic structure and function. Consistently, in human AAA specimens, decreased LH1 expression was associated with increased thrombospondin-1 levels. Conclusions: LH1 deficiency contributes to dissecting AAA pathogenesis, at least in part, by upregulating thrombospondin-1 expression, which subsequently enables proinflammatory processes, MMP activation and VSMCs apoptosis. Our study provides evidence that LH1 is a potential critical therapeutic target for AAA.

Background: Circular RNAs (circRNAs) have shown promise as biomarkers because of their stability in peripheral blood, and they participate in various pathological processes of ischemic stroke; however, their expression profiles and the potential functions for intracerebral hemorrhage (ICH) stroke remain unclear. Methods: RNA sequencing was used to investigate the expression profiles of circRNA in a discovery sample of 129 subjects (44 patients with ICH, 42 hypertension (HTN) controls, and 43 patients with cerebral infarction (CI)), and an independent validation sample of 54 subjects (20 patients with ICH, 18 HTN controls, and 16 patients with CI). Quantitative real-time polymerase chain reaction was used to validate the circRNA expression levels. Logistic regression models were conducted to assess circRNAs as potential biomarkers for ICH. Bioinformatics analysis was performed to identify potential functions of circRNAs.Results: We found that 15 circRNAs including 5 upregulated circRNAs and 10 downregulated circRNAs were consistently altered only after ICH (fold change >1.5 and FDR < 0.05). We validated that hsa_circ_0001240 and hsa_circ_0001947 were upregulated and that hsa_circ_0001386 was downregulated in ICH compared with HTN and CI. The combination of 3 circRNAs showed an area under the curve of 0.92 with a sensitivity of 86% and a specificity of 88% for diagnosing ICH. Together with ICH risk factors, the circRNAs showed an area under the curve of 0.97 in diagnosing ICH. Functional analysis revealed circRNA target miRNA and mRNA are mainly involved in fatty acid biogenesis, lysine degradation, integrin cell surface interactions and the immune system.Conclusion: This is the first report to study the expression profile of circRNAs in peripheral blood after ICH, and a set of 3 circRNAs could serve as potential biomarkers for predicting and diagnosing ICH.

BACKGROUND D-dimer tests have been widely used to rule-out deep venous thrombosis (DVT), but with low specificity. Circulating microRNAs (miRNAs) are novel promising biomarkers in diverse diseases. The purpose of our study was to identify the diagnostic abilities of circulating miRNA-320a/b and to assess their correlation with plasma D-dimer in DVT and post-thrombotic syndrome (PTS) patients. MATERIAL AND METHODS Plasma samples were taken from 30 DVT patients, 30 PTS patients, and 30 age- and sex-matched healthy volunteers. Quantitative real-time PCR (qPCR) assay and turbidimetric immunoassay were conducted to assess the concentrations of miRNA-320a/b and D-dimer in plasma. RESULTS Circulating miRNA-320a and miRNA-320b were significantly upregulated in DVT patients with fold changes of 1.58 and 1.79, respectively. The receiver operating characteristic (ROC) curve analysis showed area under the curve (AUC) values of 0.70 (95% CI: 0.56-0.83) for miRNA-320a and 0.79 (95% CI: 0.67-0.90) for miRNA-320b. Moreover, plasma levels of miRNA-320b were associated with D-dimer values (r=0.52, 95% CI: 0.19-0.74) in DVT. However, no significant changes in plasma miRNA-320a/b and D-dimer were detected in PTS patients. CONCLUSIONS Compared with controls, circulating miRNA-320a/b was differentially expressed in DVT. Simultaneous detection of miRNA-320a/b with D-dimer may improve diagnostic accuracy of DVT.

Background: Acute myocardial infarction (AMI) is one of the leading causes of mortality and morbidity worldwide. Recently, several studies have revealed the diagnostic value of circulating microRNAs (miRNAs) for AMI detection. However, the diagnostic capacity of miRNAs for AMI is still controversial due to the inconsistent results among studies. Methods: A systematic literature search was conducted to retrieve relevant articles in PubMed and other databases up to February 2017. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were used to assess the overall test performance of miRNAs. Subgroup analysis was conducted to explore the potential sources of heterogeneity. We evaluated the publication bias by the Deeks’ funnel plot asymmetry test and all statistical analyses were performed using Meta-disc 1.4 and Stata software. Results: A total of 26 articles comprising 1973 AMI patients and 1236 healthy controls were included in this meta-analysis. The overall pooled diagnostic data was as follows: the pooled sensitivity of 0.76 (95% confidence interval [CI]: 0.75–0.78), the pooled specificity of 0.82 (95% CI: 0.81–0.84), the pooled PLR of 4.68 (95% CI: 3.92–5.59), the pooled NLR of 0.28 (95% CI: 0.25–0.32), and the pooled DOR of 18.66 (95% CI: 14.11–24.68). The AUC value was 0.8661 in the overall summary receiver operator characteristic curve. Subgroup analysis indicated that miRNA-499 had better diagnostic accuracy over other miRNAs. Conclusion: MiRNAs may serve as promising diagnostic biomarkers in the early diagnosis of AMI. Further studies were needed to evaluate the diagnostic value of miRNAs for AMI before clinical application.

Background Clinically, D-dimer is the only established biomarker for the diagnosis of deep vein thrombosis (DVT). However, low specificity discounts its diagnostic value. Several publications have illustrated the differentially expressed circulating microRNAs (miRNAs) and their potential diagnostic values for DVT patients. Therefore, we systematically evaluated present researches and further performed bioinformatics analysis, to provide new insights into the diagnosis and underlying mechanisms of miRNAs in DVT. Methods Databases PubMed, Web of Science, and Embase were searched from January 2000 to April 2017. Articles on circulating miRNAs expression in DVT were retrieved and reference lists were handpicked. Bioinformatics analysis was conducted for further evaluation. Results Eventually, the eligibility criteria for inclusion in this study were met by 3 articles, which consisted of 13 specially expressed miRNAs and 149 putative target genes. Two representative KEGG pathways, vascular endothelial growth factor and phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway, seemed to participate in the regulatory network of thrombosis. Conclusions Despite the potential diagnostic value and regulation effect, the results of circulating miRNAs used as biomarkers for DVT are not so encouraging. More in-depth and larger sample investigations are needed to explore the diagnostic and therapeutic values of miRNAs for DVT.

In recent years, lymphocyte-to-monocyte ratio (LMR) has become a novel indirect marker of inflammation, which has been demonstrated to be associated with poor prognosis of oncology and cardiovascular disease. The aim of the study was to assess the relationship between LMR on admission and in-hospital and long-term major adverse cardiac and cerebrovascular events (MACCE) in patients with ST-elevated myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). A total of 306 STEMI patients were enrolled and grouped according to tertiles of LMR from the blood samples obtained in the emergency room on admission. Total white blood cell count, differential count of neutrophil, lymphocyte, monocyte, and other factors were evaluated. The median follow-up period was 21 months (1–36 months). As the LMR decreased, in-hospital nonfatal myocardial infarction and cardiovascular mortality increased (P = .002, P = .009, respectively). And long-term stroke/TIA, TVR, nonfatal myocardial infarction, and cardiovascular mortality also increased with decreasing LMR (P = .012, P = .001, P = .003, P = .002, respectively). The receiver operating characteristic (ROC) curve of LMR for predicting MACCE showed the sensitivity of 76% and specificity of 78% and the optimal cut-off value was determined as 2.62. In multivariate analysis, after adjusting for confounders, LMR was an independent predictor of in-hospital and long-term MACCE (odds ratio [OR] 1.192 [1.069–1.315] P