Identification of lncRNA-mRNA regulatory network associated with isolated systolic hypertension and atherosclerotic cerebral infarction.

BACKGROUND: Increasingly, evidence has shown that long non-coding RNAs (lncRNAs) play an important role in isolated systolic hypertension (ISH). However, a systematic lncRNA-messenger RNA (mRNA) regulatory network is still absent in isolated systolic hypertension and atherosclerotic cerebral infarction patients (ISH & ACI). This research aimed to establish a lncRNA-mRNA co-expression network in patients with ISH & ACI, to probe into the potential functions of lncRNA in such patients. METHODS: Expression profiles of lncRNA and mRNAs were collected and compared, from 8 patients with ISH and 8 patients with ISH & ACI by RNA-seq data. Differentially expressed lncRNAs and mRNAs were screened out via high-throughput sequencing in the plasma of ISH/ACI patients and control ISH patients. Then, a lncRNA-mRNA interaction network was built using the Pearson correlation coefficient by Cytoscape software. The expression levels of the hub genes and lncRNAs were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in another 10 ISH/ACI patients and 10 control patients. This study was approved by the responsible institutional review board (IRB) and informed consent was provided by participants. RESULTS: A total of 2,768 differentially expressed lncRNAs and 747 differentially expressed mRNAs were identified. We identified two hub genes (CD226 and PARVB) and 11 lncRNAs in the lncRNA-mRNA interaction network. The results of qRT-PCR and cell assay verified that lncRNAs ENST00000590604 and CD226 are highly expressed in patients of ISH & ACI. Further, CD226 was associated with vascular endothelial cells growth and stability through the platelet activation and focal adhesion pathway. CONCLUSIONS: We established a novel mRNA-lncRNA interaction network. The lncRNAs ENST00000590604 and CD226 might be the potential biomarkers of ISH & ACI.

Banxia Baizhu Tianma decoction attenuates obesity-related hypertension.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Baizhu Tianma decoction (BBTD) is a classical representative prescription for expelling phlegm, extinguishing wind, strengthening the spleen and dissipating excessive fluid in traditional Chinese medicine (TCM). According to both TCM theory and about 300 years of clinical practice, BBTD is especially suitable for hypertensive patients of abdominal obesity and lacking physical activity. AIM OF THE STUDY: The present study tried to interpret the pharmacology of the ancient formula of BBTD. Herein, we focused on the plasma metabonomics of BBTD and evaluated the effect and targets of BBTD on endothelial protective effect. METHODS: Obesity-related hypertensive mice were induced by high-fat diet for 20 weeks. BBTD (17.8 g/kg) was administered intragastrically for 8 weeks, and telmisartan group (12.5 mg/kg) was used as positive drug. Body weight, blood pressure, triglyceride and cholesterol were recorded to evaluate the efficacy of BBTD in vivo. Lipid deposition in aortic roots was assessed by oil red O staining, while morphology of aortas was observed by HE staining. Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed to study the plasma non-targeted metabonomics. According to the data of metabonomics, human aortic endothelial cells (HAECs) were treated by oxidized low-density lipoprotein (ox-LDL, 50 µg/mL) with/without BBTD (2, 1 or 0.5 mg/mL). Apoptosis rate (Annexin V-FITC/PI), migration (Transwell), cytoskeleton (Phalloidin) and density of VE-cadherin (Immunofluorescence staining) were used to investigate the effect of BBTD in vitro. Transcriptome sequencing was performed (2 mg/mL BBTD vs ox-LDL) to screen the possible targets of BBTD in endothelial protection against ox-LDL. RESULTS: BBTD effectively reduced the body weight and total cholesterol, and decreased 12.1 mmHg in SBP and 10.5 mmHg in DBP of obesity-related hypertensive mice (P < 0.05). BBTD attenuated lipid deposition in arterial roots and improved the morphology of aortas in vivo. Plasma metabolite profiles identified 94 differential metabolites and suggested BBTD mainly affected glycerophospholipids and fatty acyls. Bioinformatics analysis indicated sphingolipid metabolism and fluid shear stress and atherosclerosis were main pathways. Therefore, we focused on endothelial protective effect of BBTD against ox-LDL. In vitro, BBTD demonstrated endothelial protective effects, decreasing apoptosis rate, improving cell migration in dose-dependent manner and maintaining cell morphology. Transcriptome sequencing identified 251 downregulated and 603 upregulated mRNAs after 24h-BBTD treatment, which reversed 51.8% change in mRNAs (393 DE mRNAs) induced by ox-LDL. Bioinformatics analysis supported the potential of BBTD in hypertension and suggested that BBTD improved endothelial cells by targeting mainly on p53 and PPAR signaling pathways. CONCLUSIONS: BBTD attenuates obesity-related hypertension by regulating metabolism of glycerophospholipids and endothelial protection.

Downregulated LINC01614 Ameliorates Hypoxia/Reoxygenation-Stimulated Myocardial Injury by Directly Sponging microRNA-138-5p.

BACKGROUND: LINC01614 was abnormally expressed in myocardial infarction and other heart failures. We attempted to detect the effects of LINC01614 in myocardial ischemia-reperfusion (I/R) injury. METHODS: H9c2 cardiomyocyte cells were treated with hypoxia/reoxygenation (H/R) to establish myocardial ischemia (MI) model. RESULTS: Clinical data of Gene Expression Omnibus (GEO) database indicated that LINC01614 was highly regulated in first acute myocardial infarction, whereas miR-138-5p was downregulated in unstable angina pectoris. LINC01614 inhibition promoted cell proliferation and repressed the apoptotic property after H/R treatment using Cell Counting Kit-8 and flow cytometry analysis. Downregulation of LINC01614 enhanced the expression of Bcl-2 but attenuated Bax and cleaved caspase 3 expression after H/R treatment. Bioinformatics prediction and dual-luciferase reporter assay determined that LINC01614 directly targeted miR-138-5p and negatively regulated the expression of miR-138-5p. Furthermore, the overexpression of miR-138-5p significantly strengthened the function of si-LINC01614 in H/R groups. CONCLUSION: Our results illustrated that reduction in LINC01614 attenuated H/R treatment-induced myocardial damage via sponging miR-138-5p.