Atherosclerosis is a primary cause of multiple types of cardiovascular disease, including myocardial infarction. In addition, injury of human umbilical vein endothelial cells (HUVECs) can lead to the development of atherosclerosis. Circular (circ)RNAs participate in atherosclerosis. It has previously been shown that circRNA cSMARCA5 (hsa_ circ_0001445) expression is downregulated in atherosclerosis. However, the effects of hsa_circ_0001445 on the proliferation of HUVECs remain unclear. In order to mimic atherosclerosis in vitro, HUVECs were treated with oxidized low-density lipoprotein (oxLDL). The expression levels of specific genes and proteins were detected in HUVECs by reverse transcription-quantitative PCR and western blot analysis, respectively. Cell proliferation was assessed by Cell Counting Kit-8 and 5-Ethynyl-2'-deoxyuridine staining. Cell apoptosis and 5,5' ,6,6'-Tetrachloro-1,1' ,3,3'-tetraethyl-imidacarbocyanine staining were examined by flow cytometry. In addition, the association between hsa_circ_0001445 and serine/arginine-rich splicing factor 1 (SRSF1) was investigated by RNA pull-down assay. hsa_circ_0001445 expression was downregulated in oxLDL-treated HUVECs. Moreover, oxLDL-induced inhibition of HUVEC proliferation was significantly reversed by overexpression of hsa_circ_0001445. oxLDL notably inhibited tube formation and mitochondrial membrane potential in HUVECs, while these effects were markedly reversed by hsa_circ_0001445 overexpression. Furthermore, overexpression of hsa_circ_0001445 reversed oxLDL-induced activation of β-catenin by binding to SRSF1. Collectively, these data demonstrated that overexpression of hsa_circ_0001445 reversed oxLDL-induced inhibition of HUVEC proliferation via activation of the SRSF1/β-catenin axis. These findings may provide novel targets for the treatment of atherosclerosis.

Genes associated with specific neurocognitive phenotypes in Williams–Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams–Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams–Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient retained these genes but showed neurodevelopmental abnormalities. By comparing the genotypes and phenotypes of patients with typical and atypical deletions and previous reports in the literature, we hypothesize that the BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS.

Background The Williams-Beuren syndrome (WBS) is a multiple phylogenetic disorder, caused by the hemizygous deletion of 1.55 to 1.84 Mb on chromosome 7q11.23, which encodes a fragment of 26 to 28 genes. Among these genes, the deletion of the elastin (ELN) gene haplotype is the main cause of cardiovascular abnormalities. Other genes, such as CLIP2, GTF2IRD1, and GTF2I, may be associated with specific cognitive and craniofacial features. However, genes associated with specific neurocognitive phenotypes are still controversially discussed. The purpose of this study is to further explore the mechanism of neurodevelopmental disorders in patients with Williams-Beuren syndrome.Patients and methods Patients who had been diagnosed with WBS were recruited. The deletion was precisely defined by chromosome microarray analysis and the clinical phenotype was evaluated. Results This study identified nine patients with atypical deletions from 111 patients with WBS. One patient had normal neurodevelopmental with deletion of Williams-Beuren syndrome chromosomal region (WBSCR) telomere side genes, including GTF2I and GTF2IRD1, while another patient retained these genes but showed neurodevelopmental abnormalities. Seven of the eight patients with the WBSCR22 gene deletion developed growth restriction.Conclusions By comparing the genotype and phenotype of patients with typical deletions and atypical deletions, the deletion of GTF2I and GTF2IRD1 genes alone insufficient to induce typical neurocognitive phenotypes in WBS patients. The BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS. Furthermore, the deletion of the WBSCR22 gene may be the main cause of physical growth restriction in WBS patients.