Angiogenesis is the process by which new vessels form from existing vascular networks. Human umbilical vein endothelial cells (HUVECs) may contribute to the study of vascular repair and angiogenesis. The chemokine CXCL12 regulates multiple cell functions, including angiogenesis, mainly through its receptor CXCR4. In contrast to CXCL12/CXCR4, few studies have described roles for CXCR7 in vascular biology, and the downstream mechanism of CXCR7 in angiogenesis remains unclear. The results of the present study showed that CXCL12 dose-dependently enhanced angiogenesis in chorioallantoic membranes (CAMs) and HUVECs. The specific activation of CXCR7 with TC14012 (a CXCR7 agonist) resulted in the significant induction of tube formation in HUVECs and in vivo. Further evidence suggested that CXCL12 induced directional polarization and migration in the HUVECs, which is necessary for tube formation. Moreover, CXCR7 translocalization was observed during the polarization of HUVECs in stripe assays. Finally, treatment with TC14012 also significantly increased PI3K/Akt phosphorylation, and tube formation was blocked by treating HUVECs with an Akt inhibitor. Overall, this study indicated that CXCL12-stimulated CXCR7 acts as a functional receptor to activate Akt for angiogenesis in HUVECs and that CXCR7 may be a potential target molecule for endothelial regeneration and repair after vascular injury.

Background: Ultrafiltration decreases total body water and improves the alveolar to arterial oxygen gradient. The aims of the study were to investigate the efficacy and safety of early ultrafiltration in acute decompensated heart failure (ADHF) patients. Methods: 100 patients with ADHF within 24 h of admission were randomly assigned into early ultrafiltration (n = 40) or torasemide plus tolvaptan (n = 60) groups. The primary outcomes were weight loss and an increase in urine output on days 4 and 8 of treatment. Results: Patients who received early ultrafiltration for 3 days achieved a greater weight loss (kg) (− 2.94 ± 3.76 vs − 0.64 ± 0.91, P < 0.001) and urine increase (mL) (198.00 ± 170.70 vs 61.77 ± 4.67, P < 0.001) than the torasemide plus tolvaptan group on day 4. From days 4 to 7, patients in the early ultrafiltration group received sequential therapy of torasemide and tolvaptan. Better control of volume was reflected in a greater weight loss (− 3.72 ± 3.81 vs − 1.34 ± 1.32, P < 0.001) and urine increase (373.80 ± 120.90 vs 79.5 ± 52.35, P < 0.001), greater reduction of B-type natriuretic peptide (BNP) (pg/mL) (− 1144 ± 1435 vs − 654.02 ± 889.65, P = 0.037), NYHA (New York Heart Association) functional class (− 1.45 ± 0.50 vs − 1.17 ± 0.62, P = 0.018), jugular venous pulse (JVP) score (points) (− 1.9 ± 1.13 vs − 0.78 ± 0.69, P < 0.001), inferior vena cava (IVC) diameter (mm) (− 15.35 ± 11.03 vs − 4.98 ± 6.00, P < 0.001) and an increase in the dyspnea score (points) (4.08 ± 3.44 vs 2.77 ± 2.03, P = 0.035) in the early ultrafiltration group on day 8. No significant differences were found in the readmission and mortality rates in the 2 patient groups at the 1-month and 3-month follow-ups. Both groups had a similar stable renal profile. Conclusion: Early ultrafiltration is superior to diuretics for volume overload treatment initiation of ADHF patients. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030696, Registered 10 March 2020—Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=29099.

Angiotensin II (Ang II) is involved in the pathogenic progress of cardiovascular diseases via the promotion of abnormal proliferation and migration of human vascular smooth muscle cells (HVSMCs). Sulforaphane (SFN) exerts potent anti-inflammatory effects both in vitro and in vivo. In the present study, we aimed to investigate the effects of SFN on Ang II-induced abnormal migration of HVSMCs as well as the underlying mechanisms of those effects. The results showed that Ang II-induced HVSMC proliferation and migration were inhibited by treatment with SFN. SFN also exhibited anti-inflammatory activity, as indicated by its reduction of monocyte adhesion to HVSMCs via the reduction of ICAM1 and VCAM1 levels. Moreover, SFN reduced the Ang II-induced upregulation of HVSMC migration; this effect was inhibited by pretreatment with inhibitors of NADPH oxidase and ROS or transfection with siNOX4. In addition, SFN reversed the Ang II-induced upregulation of HVSMC migration via elevation of Nrf2 activation and expression. Taken together, the results indicate that SFN reverses Ang II-induced HVSMC migration through suppression of the NOX4/ROS/Nrf2 pathway. Thus, SFN is a potential agent to reverse the pathological changes involved in various cardiovascular diseases.

Angiogenesis is an important pathway for revascularization of ischemic tissues after acute myocardial infarction (AMI). It is unclear what role CXCR7 plays in angiogenesis in the ischemic area after AMI, although some researchers have shown that the activation of CXCR7 protectsthe heart under those conditions. Here, we hypothesize that the activation of CXCR7 promotes angiogenesis, reduces cell apoptosis and alleviates cardiac deficiency after AMI. C57BL/6 J mice were subjected to AMI and treated with TC14012 (10 mg/kg) for 24 days. HUVECs were cultured in a hypoxic (2% O2) environment to generate a model of hypoxia. CXCR7 was knocked down in HUVECs by sh-CXCR7 transfection, and CXCR7 was activated by TC14012 (30 μM) treatment. The results showed that CXCR7 was downregulated in infarcted heart tissue and hypoxic HUVECs. The global activation of CXCR7 may alleviate the decrease in cardiac function indexes - (ejection fraction and fraction shortening), and reduce infarct size after AMI.. Moreover, CXCR7 activation has been shown to enhance the level of angiogenesis in ischemic heart tissue. In vitro, hypoxia-induced angiogenic functional loss and apoptosis are aggravated by CXCR7 knockdown in HUVECs. Both angiogenic impairment and cell apoptosis are rescued by CXCR7 activation. In conclusion, the present study indicates that activation of CXCR7 plays an important protective role for ischemic cells in hypoxic endothelial cells and AMI model mice by promoting angiogenesis and reducing apoptosis, which suggests that CXCR7 may be a potential therapeutic target to rescue the ischemic myocardium..

MicroRNAs (miRNAs/miRs) are sensitive biomarkers and endogenous repressors of gene expression by decreasing mRNA stability and interfering with mRNA translation. Despite a number of investigations revealing the dysregulation of miRNA expression associated with cardiotoxicity induced by doxorubicin (Dox), perturbation of miRNAs directly resulting from Dox at early stage in cardiomyocytes and the target gene interaction remain largely unknown. In the present study, high‑throughput deep‑sequencing was used to analyze changes in global miRNA expression in H9c2 cardiomyocytes exposed to 5 µg/ml Dox for 0, 12 or 24 h. Compared with the 0‑h time point, the expression levels of 386 unique miRNAs were altered. Based on miRNA expression and fold‑change, the target genes of 76 selected miRNAs were further analyzed using gene interaction networks and pathway enrichment analysis. These miRNAs were involved in the regulation of different pathways, whose functions included apoptosis, cell proliferation, extracellular matrix remodeling, oxidative stress and lipid metabolism. These differentially expressed miRNAs included let‑7 family, miR‑29b‑3p, miR‑378‑3/5p, miR‑351‑3p, miR‑664‑3p, miR‑455‑3p, miR‑298‑3p, miR‑702‑5p, miR‑128‑1‑5p, miR‑671 and miR‑421‑5p. The present data indicated that global wide miRNA profiling in Dox‑induced cardiomyocytes may provide a novel mechanistic insight into understanding Dox‑induced heart failure and cardiotoxicity, as well as novel biomarkers and therapeutic targets.