IntroductionCurrent targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of traditional Chinese medicine Qiang-Huo (Notopterygium incisum), had shown the antiproliferative and anti-inflammatory properties in previous studies, we hypothesized that it could play a role in ameliorating PAH.MethodsIn vivo, we conducted monocrotaline (MCT) induced PAH rats and treated them with notopterol for 3 weeks. Then, the rats were examined by echocardiography and RV catheterization. The heart and lung specimens were harvested for the detection of gross examination, histological examination and expression of inflammatory molecules. In vitro, human pulmonary arterial smooth muscle cells (HPASMCs) were treated with notopterol after hypoxia; then, cell proliferation was assessed by cell counting kit-8 and Edu assay, and cell migration was detected by wound healing assays.ResultsWe found that notopterol improved mortality rate and RV function while reducing right ventricular systolic pressure in MCT-induced PAH rats. Furthermore, notopterol reduced right ventricular hypertrophy and fibrosis, and it also eased pulmonary vascular remodeling and MCT-induced muscularization. In addition, notopterol attenuated the pro-inflammatory factor (IL-1β, IL-6) and PCNA in the lungs of PAH rats. For the cultured HPASMCs subjected to hypoxia, we found that notopterol can inhibit the proliferation and migration of HPASMCs.ConclusionOur studies show that notopterol exerts anti-inflammatory and anti-proliferative effects in the pulmonary arteries, which may contribute to prevention of PAH.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the mechanism underlying cerebral dysfunction after deep hypothermic circulatory arrest (DHCA), although the exact details have not been elucidated. To explore the expression profiles of lncRNAs and miRNAs in DHCA cerebral injury, we determined the lncRNA, miRNA and mRNA expression profiles in the cerebral cortex of DHCA and sham rats. First, a rat model of DHCA was established, and high-throughput sequencing was performed to analyze the differentially expressed RNAs (DERNAs). Then, the principal functions of the significantly deregulated genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Expression networks (lncRNAs-miRNAs-mRNAs and transcription factors (TFs)-miRNAs-mRNAs) were also established. Finally, the expression of DERNAs was confirmed by quantitative real-time PCR (RT-qPCR). We identified 89 lncRNAs, 45 miRNAs and 59 mRNAs between the DHCA and sham groups and constructed a comprehensive competitive endogenous RNAs (ceRNAs) network. A TF-miRNA-mRNA regulatory network was also established. Finally, we predicted that Lcorl-miR-200a-3p-Ttr, BRD4-Ccl2 and Ep300-miR-200b-3p-Tmem72 may participate in the pathogenesis of DHCA cerebral injury.

Background This study aimed to investigate the effect of isoproterenol pre-treatment on the therapeutic efficacy of cardiosphere-derived cells (CDCs) transplantation for myocardial infarction (MI). Methods Thirty 8-week-old male Sprague-Dawley (SD) rat model of MI was generated by ligation of the left anterior descending artery. The MI rats were treated with PBS (MI group, n=8), CDCs (MI + CDC group, n=8) and isoproterenol pre-treated CDCs (MI + ISO-CDC group, n=8), respectively. In the MI + ISO-CDC group, CDCs were pre-treated by 10 −6 M isoproterenol and the cultured for additional 72 h, then injected to the myocardial infraction area like other groups. At 3 weeks after the operation, echocardiographic, hemodynamic, histological assessments and Western blot were performed to compare the CDCs differentiation degree and therapeutic effect. Results Isoproterenol treatment (10 −6 M) simultaneously inhibited proliferation and induced apoptosis of CDCs, up-regulated proteins of vimentin, cTnT, α-sarcomeric actin and connexin 43, and down-regulated c-Kit proteins (all P<0.05). The echocardiographic and hemodynamic analysis demonstrated that the MI rats in the two CDCs transplantation groups had significantly better recovery of cardiac function than the MI group (all P<0.05). MI + ISO-CDC group had better recovery of cardiac function than the MI + CDC group, although the differences did not reach significant. Immunofluorescence staining showed that the MI + ISO-CDC group had more EdU-positive (proliferating) cells and cardiomyocytes in the infarct area than the MI + CDC group. MI + ISO-CDC group had significantly higher protein levels of c-Kit, CD31, cTnT, α-sarcomeric actin and α-SMA in the infarct area than the MI + CDC group. Conclusions These results suggested that in CDCs transplantation, isoproterenol pre-treated CDCs can provide a better protective effect against MI than the untreated CDCs.