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J Mol Cell Cardiol ; 141: 82-92, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32222458


Vascular dysfunction is a common pathological basis for complications in individuals affected by diabetes. Previous studies have established that endothelial dysfunction is the primary contributor to vascular complications in type 2 diabetes (T2DM). However, the role of vascular smooth muscle cells (VSMCs) in vascular complications associated with T2DM is still not completely understood. The aim of this study is to explore the potential mechanisms associated with Ca2+ handling dysfunction and how this dysfunction contributes to diabetic vascular smooth muscle impairment. The results indicated that endothelium-dependent vasodilation was impaired in diabetic aortae, but endothelium-independent vasodilation was not altered. Various vasoconstrictors such as phenylephrine, U46619 and 5-HT could induce vasoconstriction in a concentration-dependent manner, such that the dose-response curve was parallel shifted to the right in diabetic aortae, compared to the control. Vasoconstrictions mediated by L-type calcium (Cav1.2) channels were attenuated in diabetic aortae, but effects mediated by store-operated calcium (SOC) channels were enhanced. Intracellular Ca2+ concentration ([Ca2+]i) in VSMCs was detected by Fluo-4 calcium fluorescent probes, and demonstrated that SOC-mediated Ca2+ entry was increased in diabetic VSMCs. VSMC-specific knockout of STIM1 genes decreased SOC-mediated and phenylephrine-induced vasoconstrictive response in mice aortae. Additionally, Orai1 expression was up-regulated, Cav1.2 expression was downregulated, and the phenotypic transformation of diabetic VSMCs was determined in diabetic aortae. The overexpression of Orai1 markedly promoted the OPN expression of VSMCs, whereas SKF96365 (SOC channel blocker) reversed the phenotypic transformation of diabetic VSMCs. Our results demonstrated that the vasoconstriction response of aortic smooth muscle was weakened in type 2 diabetic rats, which was related to the downregulation of the Cav1.2 channel and the up-regulation of the SOC channel signaling pathway.

Mol Phylogenet Evol ; 146: 106758, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028031


The Bambusa-Dendrocalamus-Gigantochloa complex (BDG complex) is the most diversified and phylogenetically recalcitrant group of the paleotropical woody bamboos. Species of this complex occur in tropical and subtropical Asia and most of them are of great economic, cultural and ecological value. The lack of resolution achieved through the analyses of previous molecular datasets has long confounded its phylogenetic estimation and generic delimitation. Here, we adopted a ddRAD-seq strategy to investigate phylogenetic relationships of the four main genera (Bambusa, Dendrocalamus, Gigantochloa, and Melocalamus) in the BDG complex. A total of 102 species were sampled, and SNP data were generated. Both MP and ML analyses of the ddRAD-seq data resulted in a well-resolved topology with Gigantochloa and Melocalamus confirmed as monophyletic, and Melocalamus resolved as sister to the rest of the complex. Bambusa and Dendrocalamus were both resolved as paraphyletic. The phylogenetic relationships were mostly supported by morphological evidence including characters of the branch complement, rachilla, lodicules, filaments and stigma. We also generated and assembled complete plastid genomes of 48 representative species. There were conflicts between the plastome and the ddRAD topologies. Our study demonstrated that RAD-seq can be used to reconstruct evolutionary history of lineages such as the bamboos where ancient hybridization and polyploidy play a significant role. The four genera of the BDG complex have a complex evolutionary history which is likely a product of ancient introgression events.

Mol Plant ; 12(10): 1353-1365, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31145999


Polyploidization is a major driver of speciation and its importance to plant evolution has been well recognized. Bamboos comprise one diploid herbaceous and three polyploid woody lineages, and are members of the only major subfamily in grasses that diversified in forests, with the woody members having a tree-like lignified culm. In this study, we generated four draft genome assemblies of major bamboo lineages with three different ploidy levels (diploid, tetraploid, and hexaploid). We also constructed a high-density genetic linkage map for a hexaploid species of bamboo, and used a linkage-map-based strategy for genome assembly and identification of subgenomes in polyploids. Further phylogenomic analyses using a large dataset of syntenic genes with expected copies based on ploidy levels revealed that woody bamboos originated subsequent to the divergence of the herbaceous bamboo lineage, and experienced complex reticulate evolution through three independent allopolyploid events involving four extinct diploid ancestors. A shared but distinct subgenome was identified in all polyploid forms, and the progenitor of this subgenome could have been critical in ancient polyploidizations and the origin of woody bamboos. Important genetic clues to the unique flowering behavior and woody trait in bamboos were also found. Taken together, our study provides significant insights into ancient reticulate evolution at the subgenome level in the absence of extant donor species, and offers a potential model scenario for broad-scale study of angiosperm origination by allopolyploidization.

Genômica , Poaceae/genética , Poaceae/metabolismo , Madeira/metabolismo , Flores/crescimento & desenvolvimento , Genoma de Planta/genética , Anotação de Sequência Molecular , Poaceae/crescimento & desenvolvimento , Poliploidia
J Mol Cell Cardiol ; 122: 134-139, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30118789


Circular RNAs (circRNAs), a large novel type of endogenous transcripts, have become a new research hotspot in the field of RNA biology. CircRNAs are mainly generated from exons or introns via multiple mechanisms, and the majority of circRNAs are stable and conserved across different species. Recent studies have revealed that circRNAs can function as miRNA sponges, binding partners of proteins, regulators of transcription, or can even be translated into proteins. Growing evidence has demonstrated that circRNAs play important roles in a wide variety of biological processes such as cell proliferation, apoptosis and senescence, and may serve as potential diagnostic biomarkers or therapeutic targets for various cardiovascular diseases. Here, we review the biogenesis, properties and biological function of circRNAs, and summarize their roles in cardiovascular disorders.

Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Processamento Alternativo , Apoptose , Sítios de Ligação , Biomarcadores/metabolismo , Proliferação de Células , Regulação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Miócitos de Músculo Liso/fisiologia , Ligação Proteica , Biossíntese de Proteínas
Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-29654172


Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In a multivariate logistic regression analysis, we detected an association of rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02-2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01-2.36, P=0.043) were statistically significantly associated with the increased risk for CAD. A similar trend of the association was found in dominant model (OR = 1.53, 95% CI = 1.05-2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03-1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased plasma ET-1 levels compared with TT genotype (P<0.05). No association of the other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our study provides the first evidence that EDN1 tagSNP rs6458155 is associated with CAD risk in the Chinese Han population, which is probably due to the influence of the circulating ET-1 levels.

Doença da Artéria Coronariana/genética , Endotelina-1/genética , Polimorfismo de Nucleotídeo Único , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Endotelina-1/sangue , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
Lipids Health Dis ; 17(1): 7, 2018 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-29304813


BACKGROUND: Accumulating evidences have shown that miRNAs are directly or indirectly involved in a variety of biological processes, and closely associated with diverse human diseases, including cardiovascular diseases. SNPs locating within pri/pre-miRNA can affect miRNA processing and binding ability of target genes. MiR-27a, miR-26a-1 miR-100, miR-126 and miR-218 were reported to be associated with pathogenesis of myocardial infarction (MI). Here we aimed to evaluate the potential association of five polymorphisms in these pri/pre-miRNAs with individual susceptibility to MI in a Chinese Han population. METHODS: Genotyping was performed in 287 MI cases and 646 control subjects using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The association of these SNPs with MI risk was performed with SPSS software. RESULTS: In a logistic regression analysis, we found that AG heterozygote (OR = 0.40, 95% CI = 0.21-0.76, Pa = 0.005) or AA homozygote (OR = 0.40, 95% CI = 0.22-0.75, Pa = 0.004) of pre-miR-27a rs895819 had a reduced susceptibility to MI in comparison with GG homozygote. Similarly, a reduced risk of MI was detected when the AG and AA genotypes were combined (OR = 0.40, 95% CI = 0.22-0.74, Pa = 0.003). However, no significant association between pri-miR-26a-1 pri-miR-100, pri-miR-126 and pri-miR-218 polymorphisms and MI risk was observed under the allelic and established genetic models. Further stratified analysis of pre-miR-27a rs895819 revealed a more significant association of AG + AA genotypes with MI risk among younger, male and smoking subjects. Interestingly, AG and AA genotypes of the rs895819 polymorphism conferred about 0.17 mmol/L and 0.18 mmol/L increase in HDL-C levels compared to GG genotype. CONCLUSIONS: Our findings suggest that the pre-miR-27a rs895819 polymorphism is associated with MI susceptibility in the Chinese Han population, which probably due to influence the HDL-C levels.

Predisposição Genética para Doença , MicroRNAs/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Heterozigoto , Homozigoto , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Razão de Chances , Fatores de Risco