Effectiveness and mechanism of Huoxin pill on heart failure after percutaneous coronary intervention: Study protocol for a double-blind, randomised, placebo-controlled parallel trial.

Background: Coronary heart disease (CHD) is the most common cardiovascular disease facing human beings. Cardiac remodelling is an important pathological factor for the progression of heart failure (HF) after CHD. At present, Chinese medicine is widely used in the treatment of HF, but there are still some drugs lack of evidence-based and mechanism evidence. Multi-omics techniques can deep explore candidate pathogenic factors and construct gene regulatory networks.This trial is intended to evaluate the effect on Huoxin pill (HXP) in the treatment of HF after programmable communication interface (PCI). Meantime, multi-omics analysis technique will be used to target the fundamental pathological links of cardiac remodelling, so as to study the mechanism of HXP in the treatment of HF after PCI. Methods: This study is a randomized, double-blind, placebo-controlled trial. Sixty patients with HF undergoing PCI are recruited from the First Affiliated Hospital of Henan University of CM. All selected patients will be randomly attributed to receive conventional treatment + HXP or placebo. The packaging, dosage and smell of placebo and heart activating pill were identical. The primary outcome is NYHA cardiac function grade, while the secondary outcomes included Lee's HF score, exercise tolerance test, and quality of life evaluation. Additional indicators include cardiac ultrasound, electrocardiogram, 24-h dynamic electrocardiogram, myocardial injury indicators, and energy metabolism indicators. Discussion: This study may provide a new treatment option for patients with HF after PCI and provide evidence for the treatment of CHD and HF with HXP. Trial registration: 2023-10-08 registered in China Clinical Trial Registry, registration number ChiCTR2300076402.

Inhibition of BAG-1 induced SH-SY5Y cell apoptosis without affecting Hsp70 expression.

OBJECTIVE: To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). METHODS: RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. RESULTS: BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. CONCLUSION: BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.

Hirudin promotes angiogenesis by modulating the cross-talk between p38 MAPK and ERK in rat ischemic skin flap tissue.

Hirudin's ability to increase angiogenesis in ischemic flap tissue and improve the flaps survival has been demonstrated in our previous studies. However, the knowledge about hirudin functional role in angiogenesis is still limited. In the present study, we investigate the effects of locally injected hirudin on the expression of VEGF, endostatin and thrombospondin-1 (TSP-1) using rat model. Caudally based dorsal skin flaps were created and were treated with hirudin or normal saline. Result showed that the flap survival was improved by hirudin treatment relative to the control. Treatment of flaps with hirudin exerted significant angiogenic effect as evidenced by increased VEGF expression and reduced endostatin and TSP-1 production (p<0.01), and promoted neovascularization (microvascular density, p<0.01). Moreover, hirudin treatment increased the ERK1/2 phosphorylation, while attenuated the phosphorylation of p38 MAPK, and the addition of thrombin could reverse these effects of hirudin on ERK1/2 and p38 MAPK activity. The MEK inhibitor blocked the hirudin-induced VEGF expression, and the p38 MAPK inhibitor attenuated the thrombin-induced TSP-1 expression. Furthermore, a specific inhibitor of p38 MAPK activates ERK1/2 in ischemic flaps, suggesting that cross-talk between p38 MAPK and ERK might exist in rat ischemic flap tissue. Moreover, either the hirudin or SCH79797 (PAR1 antagonist) could attenuate the p38 MAPK phosphorylation and increases the ERK1/2 phosphorylation, indicating that the cross-talk between p38 MAPK and ERK1/2 modulated by thrombin/PAR1 signaling may participate in the process of hirudin-stimulated ERK1/2 signaling. In conclusion, these observations suggest that hirudin exerts its angiogenesis effect by regulating the expression of angiogenic and antiangiogenic factors via a cross-talk of p38 MAPK-ERK pathway.