In-stent restenosis (ISR) is the main factor affecting the outcome of percutaneous coronary intervention (PCI), and its main pathological feature is neointimal hyperplasia. Huotan Jiedu Tongluo decoction (HTJDTLD) is an effective traditional Chinese medicine (TCM) prescription for the treatment of vascular stenosis diseases. However, the precise anti-ISR mechanism of HTJDTLD remains unclear. Here, we investigated whether HTJDTLD can inhibit the excessive activation of endoplasmic reticulum stress (ERS) and reduce the level of autophagy factors through regulating the PERK-eIF2α-ATF4 pathway, thereby inhibiting the proliferation of the intima of blood vessels damaged by balloon injury (BI) and preventing the occurrence of ISR. In this study, a 2F Fogarty balloon was used to establish a common carotid artery (CCA) BI model in male Sprague-Dawley rats. Then, HTJDTLD (16.33 g/kg/d) or atorvastatin (1.19 mg/kg/d) was administered by gavage. Four weeks later, hematoxylin-eosin (HE) and Masson staining of the injured CCA were performed to observe the histological changes in the CCA. Immunohistochemistry (IHC) was used to assess the proliferation and dedifferentiation of vascular smooth muscle cells (VSMCs) in the CCA. Western blotting and RT-PCR were used to measure the expression of ERS- and autophagy-related proteins and mRNAs in the CCA. The results indicated that HTJDTLD significantly alleviated BI-induced carotid artery intimal hyperplasia and fibrosis and reduced the neointimal area (NIA) and NIA/medial area (MA) ratio. In addition, HTJDTLD inhibited the proliferation and dedifferentiation of VSMCs, reduced the expression of proliferating cell nuclear antigen (PCNA), and increased the smooth-muscle-α-actin- (SMα-actin-) positive area. HTJDTLD also significantly reduced the expression of the ERS-related factors: GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, and CHOP. In addition, the expression of the autophagy-related factors, Beclin1, LC3B, and ATG12, was significantly decreased. In addition, in vitro experiments showed that HTJDTLD inhibited the above-mentioned ERS signal molecules in human umbilical vein endothelial cells (HUVEC) and rat aortic smooth muscle cells (A7R5) induced by tunicamycin (TM) and played a crucial role in protecting cells from damage. HTJDTLD may be a very promising drug for the treatment of ISR.

Background: In recent years, with the increase of patients with coronary heart disease, the number of patients with heart failure (HF) has also gradually increased. Coronary heart disease is one of the most common causes of HF. Anxiety and depression are frequent psychological disorders in patients with HF. Studies have shown that anxiety and depression can affect the quality of life of patients with HF, and can increase hospitalization and mortality. Conventional pharmacotherapy and psychotherapy have certain limitations. Acupuncture has therapeutic effects on heart disease, anxiety and depression, and has been widely used to relieve symptoms in patients with HF. This protocol aims to evaluate the safety and efficacy of acupuncture for anxiety and depression in patients with HF. Methods: We will search the following databases: PubMed, Web of Science, Springer Cochrane Library, EMBASE, MEDLINE, WHO international clinical trials registry platform, China National Knowledge Infrastructure database, Wan Fang database, Chinese scientific journal database and Chinese Biomedical Literature Database. The databases will be searched from initiate to October 1, 2022. Two reviewers will screen and document eligible studies based on inclusion and exclusion criteria. Two reviewers will independently perform data analysis and bias risk assessment. Review Manager version 5.4 software will be used for meta-analysis. Results: This study will explore the efficacy and safety of acupuncture for anxiety and depression in patients with HF. Conclusion: The results of this study will provide high-quality evidence for evaluating the safety and efficacy of acupuncture for anxiety and depression in patients with HF.