circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a.

BACKGROUND: Aortic dissection (AD) is a threatening and catastrophic vascular disease with high mortality rate and limited therapeutic strategies. There is emerging evidence showing that circular RNAs play crucial role in regulating various cardiovascular diseases. However, the biological functions and molecular mechanisms of circRNAs in AD still remains elusive. The purpose of this study was to illustrate the potential functional roles and mechanisms of hsa_circ_TGFBR2 in vitro and in vivo. METHODS: The vascular smooth muscle cells (VSMCs) and AD-VSMCs were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, miR-29a and KLF4 were detected by realtime polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). Cell proliferation was assessed by CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed to identify the interaction between circ_TGFBR2 and miR-29a or between miR-29a and KLF4. The wild-type sequence of circ_TGFBR2 or KLF4 were cloned into the luciferase reporter plasmid, and the activity was measured using dual-luciferase reporter assay system. And for RNA pulldown, the relative RNA enrichment of circ_TGFBR2 and miR-29a were confirmed using RT-PCR. Western Blot measured the expression of phenotype switch-related proteins. AD rat model induced by ß-aminopropionitrile monofumarate (BAPN) was used to verify the role and mechanism of circ_TGFBR2. RESULTS: Circ_TGFBR2 inhibited cell proliferation and migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the expression of contractile markers (α-SMA, SM22α) and inhibited the expression of synthetic markers (MGP, OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge for miR-29a targeting KLF4. MiR-29a mimics rescued biological roles induced by circ_TGFBR2 overexpression. The in vivo experiments revealed that overexpression of TGFBR2 suppressed the progression of AD and increased the expression of contractile markers while inhibited the expression of synthetic markers. CONCLUSION: Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch and suppressed the progression of AD.

Circ_nuclear factor I X (circNfix) attenuates pressure overload-induced cardiac hypertrophy via regulating miR-145-5p/ATF3 axis.

Cardiac hypertrophy can cause heart failure. However, the mechanisms underlying the progression of cardiac hypertrophy remain unclear. Emerging evidence suggests that circular RNAs (circRNAs) play a critical role in cardiac hypertrophy. However, the association between circ_nuclear factor I X (circNfix) and cardiac hypertrophy remain largely unknown. Therefore, the aim of the present study was to explore the role of circNfix in cardiac hypertrophy. In order to detect the function of circNfix in cardiac hypertrophy, cardiomyocytes were stimulated with angiotensin II (Ang II) to mimic the pathogenesis of the disease. In addition, pressure overload-induced cardiac hypertrophy in a mouse model was established using transverse aortic constriction (TAC) surgery. The mechanism via which circNfix regulated cardiac hypertrophy was investigated using RNA pull-down and luciferase reporter assays, and fluorescence in situ hybridization (FISH). circNfix was downregulated in Ang II-treated cardiomyocytes. Similarly, circNfix expression was markedly downregulated in mice following TAC surgery. In addition, circNfix overexpression significantly prevented the progression of cardiac hypertrophy in TAC-treated mice. Luciferase activity and RNA pull-down assays indicated that circNfix could indirectly target activating transcription factor 3 (ATF3) by binding with microRNA (miR)-145-5p in cardiomyocytes. miR-145-5p overexpression or ATF3 knockdown could reverse the effects of circNfix in Ang II-treated mouse cardiomyocytes. circNfix attenuated pressure overload-induced cardiac hypertrophy by regulating the miR-145-5p/ATF3 axis. Therefore, circNfix may serve as a molecular target for cardiac hypertrophy treatment.

Erratum: Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart.

This corrects the article DOI: 10.1038/srep20077.

Simultaneous hybrid coronary revascularization versus off-pump coronary artery bypass grafting for diabetic patients with multivessel coronary artery disease / 中国胸心血管外科临床杂志

@#Objective    To compare the in-hospital and midterm outcomes after simultaneous hybrid coronary revascularization (HCR) with off-pump coronary artery bypass grafting (OPCAB) in diabetic patients with multivessel coronary artery disease. Methods    One hundred thirty-two diabetic patients with multivessel coronary artery disease underwent one-stop HCR at Fuwai Hospital from January 2010 to January 2015. These patients were 1∶2 matched with those who underwent OPCAB using propensity score matching. Results    Simultaneous HCR had less chest tube drainage (618 (420, 811) ml vs. 969 (711, 1 213)ml, P<0.001), lower transfusion rate (19.7% vs. 34.1%, P=0.026), shorter mechanical ventilation time (11.6 (8.2, 14.8) h vs. 16.0 (12.1, 18.7) h, P<0.001), and shorter stay in intensive care unit (21.5 (18.8, 42.0)   h vs. 44.6 (23.7, 70.1) h, P<0.001) than OPCAB. During over median 40 months follow-up, simultaneous HCR offered similar major adverse cardiac or cerebrovascular events (MACCE) rate (6.8% vs 9.0%, P=0.826), but lower stroke rate (0%vs 3.0%, P=0.029), compared with OPCAB. Conclusion    For selected patients with diabetes, simultaneous HCR provides a safe and effective revascularization alternative. It decreases perioperative invasiveness and incurred similar and favorable midterm outcomes with OPCAB.

Prolactin mediates effects of chronic psychological stress on induction of fibrofatty cells in the heart.

Cardiocyte apoptosis plays an important role in the pathogenesis of heart diseases. The mechanism is unclear. It is reported that prolactin (PRL) is involved in cardiac disorders. This study aims to investigate the role of PRL in mediating the psychological stress-induced fibrofatty cell differentiation in the heart. In this study, BALB/c mice were treated with a 30-day restraint stress. The heart tissue was processed by paraffin embedding and hematoxylin and eosin. The expression of Sca1 in NIH3T3 cells was assessed by cell culture, flow cytometry and Western blotting. The results showed that chronic stress induced fibrofatty cells in the mouse heart and high serum PRL levels. The induction of fibrofatty cell was mimicked by administration with recombinant PRL. The stress also induced the expression of Sca1 in the mouse heart. Exposure of NIH3T3 cells (a fibroblast cell line) to PRL in the culture enhanced the expression of stem cell antigen-1 (Sca1), phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of adipocyte-related protein molecules, including adiponectin, fatty acid binding protein (aP2), peroxisome proliferator activated receptor-g (PPARg) and CCAAT/enhancer binding protein (C/EBP)α, in the cells. We conclude that psychological stress-derived PRL induces fibroblasts to differentiate into fibrofatty cells in the heart.

One-stop hybrid coronary revascularization versus off-pump coronary artery bypass in patients with diabetes mellitus.

OBJECTIVES: To compare in-hospital and midterm outcomes after one-stop hybrid coronary revascularization (HCR) and off-pump coronary artery bypass (OPCAB) in patients with diabetes mellitus (DM). METHODS: The series included 120 patients with DM who underwent one-stop HCR at Fuwai Hospital between June 2007 and September 2014. These patients were 1:2 matched with 240 patients who underwent OPCAB using propensity score matching. The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE) over midterm follow-up, and secondary endpoints were in-hospital outcomes. Accounting for matched-pairs design, the survival analysis was evaluated with a marginal Cox model, and the continuous and dichotomous variables of in-hospital outcomes were compared with the Wilcoxon signed-rank test and a logistic regression model using generalized estimating equations, respectively. RESULTS: Compared with OPCAB, one-stop HCR was associated with less chest tube drainage (median, 748 mL [interquartile range (IQR), 540-1080 mL] vs 990 mL [IQR, 730-1250 mL]; P < .001), a lower packed red blood cell transfusion rate (18.3% vs 29.6%; P = .032), shorter mechanical ventilation time (median, 13.7 hours [IQR, 10.3-16.9 hours] vs 16.8 hours [IQR, 13.0-19.6 hours]; P < .001), and shorter stay in intensive care unit (median 21.7 hours [IQR, 19.0-44.3 hours] vs 46.7 hours [IQR, 24.3-72.7 hours]; P < .001). Over 30 months of follow-up, one-stop HCR and OPCAB had a similar rate of MACCE (7.4% vs 8.0% at 3 years; hazard ratio, 0.807; 95% confidence limit, 0.352-1.849; P = .612), but one-stop HCR had a lower stroke rate (0% vs 3.6% at 3 years; P = .046). CONCLUSIONS: For selected patients with DM, one-stop HCR provided safe and reproducible revascularization, with less perioperative invasiveness and similar and favorable midterm outcomes compared with OPCAB.

Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart.

To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4(+) T cells to express Fork head protein-3 and transforming growth factor (TGF)-ß via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4(+) T cells. Administration with the donor-derived exosomes significantly prolonged the allograft heart survival. We conclude that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implicating that administration with the donor-derived exosomes may be beneficial to cardiac transplantation.

Processing of the explanted heart.

Analysis of the explanted hearts from heart transplant recipients provides valuable clinical samples, which can be used to study the anatomy and pathology of the heart. PubMed database was employed as the article source of this review. This article summarized the processing methods of the explanted heart, including dissection, histopathologic examination, cryopreservation, and genetic testing. A standard processing of explanted hearts ensures the quality and reliability of samples. Analysis of explanted hearts facilitates the diagnostic assessment and therapy strategy of heart diseases.