Vascular smooth muscle cells (VSMCs) were prepared from thoracic aortas of male Sprague-Dawley rats by the explant method to observe VSMC proliferation via phosphoinositide 3 kinase (PI3K)/Akt signaling transduction pathway induced by apelin-13. Expression of PI3K, phospho-PI3K, phospho-Akt, ERK1/2, phospho-ERK1/2 and cyclin D1 was detected by western blot analysis. Results showed that apelin-13 promoted the expression of phospho-PI3K and phospho-Akt in dose- and timedependent manner. PI3K inhibitor LY294002 significantly decreased the expression of phospho-PI3K, phospho-Akt, phospho-ERK1/2, and cyclin D1 induced by apelin-13. The Akt inhibitor 1701-1 significantly diminished the expression of phospho-Akt, phospho-ERK1/2, and cyclin D1 stimulated by apelin-13. MTT assay results showed that PI3K inhibitor LY294002 and Akt inhibitor 1701-1 significantly inhibited the VSMC proliferation induced by apelin-13. Apelin-13 promoted VSMC proliferation through PI3K/Akt signaling transduction pathway.

Apelin and Elabela (ELA) are endogenous ligands of angiotensin domain type 1 receptorassociated proteins (APJ). Apelin/ELA-APJ signal is widely distributed in the cardiovascular system of fetuse and adult. The signal is involved in the development of the fetal heart and blood vessels and regulating vascular tension in adults. This review described the effects of apelin/ELA-APJ on fetal (vasculogenesis and angiogenesis) and adult cardiovascular function [vascular smooth muscle cell (VSMC) proliferation, vasodilation, positive myodynamia], and relative diseases [eclampsia, hypertension, pulmonary hypertension, heart failure (HF), myocardial infarction (MI), atherosclerosis, etc.] in detail. The pathways of apelin/ELA-APJ regulating cardiovascular function and cardiovascular-related diseases are summarized. The drugs developed based on apelin and ELA suggests APJ is a prospective strategy for cardiovascular disease therapy.

No abstract

Circular RNA (circRNA) is an important factor for regulating the progression of many cardiovascular diseases, including acute myocardial infarction (AMI). However, the role of circ_0124644 in AMI progression remains unclear. Hypoxia was used to induce cardiomyocytes injury. The expression of circ_0124644, microRNA (miR)-590-3p, and SRY-box transcription factor 4 (SOX4) mRNA was measured by qRT-PCR. Cell counting kit 8 (CCK8) assay and flow cytometry were utilized to detect cell viability, cell cycle progression, and apoptosis. The protein levels of apoptosis markers and SOX4 were determined by western blot (WB) analysis, and the levels of oxidative stress markers were assessed using commercial Assay Kits. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were employed to confirm the interaction between miR-590-3p and circ_0124644 or SOX4. Circ_0124644 was upregulated in AMI patients and hypoxia-induced cardiomyocytes. Hypoxia could inhibit cardiomyocytes viability, cell cycle process, and promote apoptosis and oxidative stress, while silencing circ_0124644 could alleviate hypoxia-induced cardiomyocytes injury. In terms of mechanism, circ_0124644 could target miR-590-3p. MiR-590-3p overexpression could relieve hypoxia-induced cardiomyocytes injury. Also, the suppressive effect of circ_0124644 knockdown on hypoxia-induced cardiomyocytes injury could be reversed by miR-590-3p inhibitor. Moreover, SOX4 was found to be a target of miR-590-3p, and its overexpression also could reverse the regulation of miR-590-3p on hypoxia-induced cardiomyocytes injury. Circ_0124644 silencing could alleviate hypoxia-induced cardiomyocytes injury by regulating the miR-590-3p/SOX4 axis, suggesting that it might be a target for alleviating AMI.

No abstract

Background: Chrysin is a natural flavonoid which has been identified as a candidate anti-cancer agent due to its inhibitory effect on a variety of cancer cells, including targeted inhibition of sphere formation in hepatocellular carcinoma (HCC) cell lines. However, the mechanism by which chrysin modulates HCC spheres remains unclear. Materials and methods: In this study, we investigate the effect of chrysin on the regulation of SHP-1 and its downstream signal molecule STAT3 to explain the mechanism by which chrysin inhibits sphere formation of HCC cell lines. Results: Here, we found that SHP-1 protein expression was markedly down-regulated in the spheres from both SMMC-7721 and MHCC97H cells. Chrysin significantly inhibited sphere formation and upregulated the expression of SHP-1 protein in both SMMC-7721 and MHCC97H cells, as well as reduced p-STAT3 and Twist1 expressions in SMMC-7721 cells. Furthermore, knockdown of SHP-1 in SMMC-7721 cells resulted in the induction of p-STAT3 and Twist1 protein expression and antagonizing the inhibitory effect of chrysin on sphere formation in SMMC-7721 cells. Conclusion: Overall, the study findings demonstrated that chrysin acts as a candidate for the treatment of HCC through modulating SHP-1/STAT3 signaling pathway.

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李兰芳 2) 苏桃 2) 陈临溪 2)***( 1) 南华大学附属第一医院心内科，衡阳 421001； 2) 南华大学药物药理研究所，衡阳 421001) 摘要 研究自发性高血压大鼠(spontanouslyhypertensiverat，SHR)离体血管环对 G 蛋白偶联受体 APJ 的内源性配体 apelin-13 的血管收缩与舒张反应及其与一氧化氮(NO)和 ERK1/2 通路关系． 采用离体血管环体外灌流方法用 Power-Lab 生物信息采集 仪检测血管环的张力． 实验分组如下：新福林(Phenylephrine，PE)组，乙酰胆碱(acetylcholine， Ach)组，apelin-13 组， apelin-13 + PE 组，apelin-13 + Ach 组，PD98059(ERK1/2 抑制剂)+ PE 组，PD98059 + Ach 组，LNNA(L-nitro-arginine，硝基左 旋精氨酸，一氧化氮合酶抑制剂) +PE 组，LNNA+Ach 组，apelin-13(预孵育) + PD98059 + PE 组，apelin-13(预孵育)+PD98059+ Ach 组，apelin-13(预孵育)+ LNNA + PE 组和 apelin-13(预孵育)+LNNA + Ach 组，以 WKY 大鼠血管环为对照组． 培养大鼠血 管平滑肌细胞，Westernblot 检测 ERK1/2 蛋白表达． 结果显示：a． apelin-13 对于有内皮的血管表现出浓度依赖性舒张作用， 血管舒张百分比 SHRWKY 大 鼠，apelin-13 预孵育，能减少 SHR 和 WKY 大鼠血管对新福林的缩血管反应性，增加对乙酰胆碱的舒张反应性；b． NOS 抑 制剂 LNNA 阻断 NO 形成后，血管环对 apelin-13 的舒张反应明显抑制，且 SHR 组较 WKY 组对 apelin 的舒张反应减少更明 显，提示 apelin-13 的舒血管效应至少部分依赖 NO 通路，而 SHR 高血压大鼠 NO 通路障碍减弱了 apelin 对血管的舒张作用； c． ERK1/2 抑制剂 PD98059 预孵育后血管环对 apelin-13 表现出浓度依赖性的收缩，与去除内皮后 apelin-13 的收缩血管效应 趋势一致，血管收缩张力 SHR＞ WKY 大鼠，PD98059 逆转了 apelin-13 引起的血管舒张效应；d． Apelin-13 促大鼠 VSMCs ERK1/2 磷酸化增加并呈剂量依赖性和时间依赖性，ERK1/2 抑制剂 PD98059 可以减少 apelin-13 诱导 ERK1/2 的磷酸化． 结 果表明，自发性高血压大鼠离体血管环对 apelin-13 舒张反应性降低， NO 通路和 ERK1/2 通路介导了 apelin-13 的舒张血管 作用． 关键词 apelin-13，APJ，一氧化氮合酶，自发性高血压大鼠，细胞外信号调节激酶 1/2(ERK1/2) 学科分类号 Q4，R36，R9