Alu元件可提高circRNA形成的效率并影响基因的表达。本课题组前期研究发现，广西巴马人群血清circ_722表达水平随年龄的增大而升高，且与多项心血管危险指标密切相关，同时受Alu元件某些多态性的影响，故推测circ_722侧翼Alu元件的序列多态性可能是心血管疾病的遗传学基础之一。鉴此，本项目拟使用PCR-Sanger测序及RT-qPCR技术对高血压及冠心病患者的circ_722 Alu元件序列多态性位点及血清表达水平进行检测，并在培养的血管内皮细胞中沉默和过表达circ_722，了解其对血管内皮细胞功能的影响，同时通过CRISPR/Cas9基因编辑技术对重要位点进行定点突变，进一步明确circ_722与Alu元件序列多态性的关系，最终从临床、细胞功能以及分子机制多个层面诠释circ_722表达在心血管疾病中的作用及其机制，期冀为心血管病的防治开辟新的视角。

Alu elements, a group of short nuclear elements interspersed in mammalian genome, are believed to increase the formative efficiency of circular RNA (circRNA). Our pilot study revealed that the serum expression of circ_722, a fragment of circRNA with 219bp in length which is derived from the back splicing of the exon 3 of GSE1 gene and is mapped to chr16:85667520-85667738 (hg19), was elevated with age in the elderly reside in Guangxi Bama County, a well known longevous region, and was dramatically linked to several cardiovascular risks. Furthermore, this change in expression was influenced by some genetic variants in Alu elements. We thus hypothesize that the polymorphism in the flank Alu elements of circ_722 may involve in the pathogenesis of cardiovascular diseases. To test this supposition, we aim to, in patients with hypertension and with coronary heart disease, define the polymorphism of circ_722 Alu element with PCR-Sanger sequencing and evaluate the serum expression level of circ_722 with RT-qPCR; in cultured endothelial cell line, silence and overexpress circ_722 to determine its impacts on the function of endothelial cells; site-direct mutate affected locus with CRISPR/Cas9 gene editing technique to further clarify the correlation between circ_722 and Alu element polymorphism. These data may promise to provide insights into the potential roles and corresponding mechanisms of circ_722 in the pathogenesis of cardiovascular diseases from clinical, cellular and molecular visions, in an attempt to open a new window for the prevention and treatment of these frustrated age-related disorders.