RESUMO
Aim: Particulate matter 2.5 (PM2.5) exposure is high risk to cardiovascular diseases. We investigated the influence of PM2.5 exposure on pulmonary arterial hypertension (PAH) murine model induced by left ventricular (LV) failure. Methods: Thirty 10 weeks old C57BL/6 mice were randomised to four groups: sham group, sham + PM2.5 group, TAC group, and TAC + PM2.5 group. Eight weeks post TAC surgery, right ventricular (RV) and lung remodelling (Sirius Red staining and WGA Staining), heart and lung function (EF and RVSBP), and fibrotic genes (TGF-ti mRNA expression and collagen III protein level in lung tissue were measured. Results: Exposure to PM2.5 augments TAC induced PAH as evidenced by decreased EF value and increased RVSBP, RV cardiomyocytes size, RV and lung fibrosis, and upregulated expression of collagen III and TGF-a in comparison to TAC group in lung tissues. Even the LV EF value was deceased from 79.3 ± 3.4% to 63.4 ± 2.1% when sham group exposed to PM2.5, PM2.5 exposure had no effect on RVSBP, RV cardiomyocytes' size, RV weight/tibia length, RV and lung fibrosis, and expression of collagen III and TGF-a in sham surgery mice. Conclusions: Exposure to PM2.5 aggravates deterioration of LV failure induced PAH.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Pressão Arterial , Insuficiência Cardíaca/complicações , Material Particulado/toxicidade , Hipertensão Arterial Pulmonar/etiologia , Artéria Pulmonar/fisiopatologia , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda , Animais , Colágeno Tipo III/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Insuficiência Cardíaca/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Exposição por Inalação , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , Hipertensão Arterial Pulmonar/fisiopatologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Fator de Crescimento Transformador beta/metabolismo , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Increasing evidences have revealed the important role of circular RNAs (circRNAs) in cardiovascular system disease. Whereas, the expression profiles and in-depth regulation of circRNAs on vascular smooth muscle cells (VSMCs) is still undetermined. In present study, our research team performed circRNAs microarray analysis to present the circRNAs expression profiles in high glucose induced VSMCs in vitro. Results showed that total of 983 circRNAs were discovered to be differentially expressed, and of these, 458 were upregulated and 525 were downregulated. Moreover, 31 circRNAs were up-regulated and 22 circRNAs were down-regulated with 2 fold change (P < 0.05). One of an up-regulated circRNA, circWDR77, was identified. In vitro cell assay, circWDR77 silencing significantly inhibited the proliferation and migration. Bioinformatics methods discovered that miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of circWDR77. The RNA sequence complementary binding was validated by RNA immunoprecipitation (RIP) and/or luciferase reporter assay. Further function validation experiments revealed that circWDR77 regulated VSMCs proliferation and migration via targeting miR-124/FGF2. Taken together, present study firstly reveals the circRNAs expression profiles in high glucose induced VSMCs and identifies the role of circWDR77-miR-124-FGF2 regulatory pathway in VSMCs proliferation and migration, which might provide a new theoretical basis for diabetes mellitus correlated vasculopathy.
Assuntos
Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , RNA/genética , RNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Sequência de Bases , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Células Cultivadas , Células HEK293 , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Circular , TranscriptomaRESUMO
The present study aimed to investigate whether diminazene attenuates myocardial infarction (MI) in rats. In addition, the present study investigated whether ACE2 signaling was involved in the effects of diminazene on protein function. A rat model of acute myocardial infarction (AMI) was established by occlusion of the left anterior descending coronary artery. The AMI model rats received intraperitoneal injections of diminazene (5 mg/kg/day) for 3 days. Treatment with diminazene significantly inhibited the expression of casein kinase and lactate dehydrogenase, and reduced infarct size in AMI rats. The findings indicated that diminazene significantly reduced the levels of inflammatory factors including tumor necrosis factorα and interleukin6, suppressed the protein expression of cytochrome c oxidase subunit 2 (COX2) and inducible nitric oxide synthase (iNOS), and activated angiotensinconverting enzyme 2 (ACE2), angiotensin II receptor type 1 (AT1R) and MAS1 protooncogene, G proteincoupled receptor (MasR) protein expression in AMI model rats. In conclusion, the present study demonstrated that diminazene attenuated AMI in rats via suppression of inflammation, reduction of COX2 and iNOS expression, and activation of the ACE2/AT1R/MasR signaling pathway.