The pandemic of Coronavirus Disease 2019 (COVID-19) has developed rapidly in the world. According to earlier reports, people over 65 years of age with cardiovascular diseases (CVD) basis such as coronary heart disease or high blood pressure are more likely to be infected and have more severe symptoms. In recent years, researches on CVDs caused by blood stasis have been increasing. Studies believe that blood stasis is not only an important pathological product of this disease, but also a pathogenic factor[2, 3]. CVD is a systemic disease in which multiple genetic inheritance interacts with the environment and multiple risk factors. It is the most common and a major public health problem worldwide. The main pathological feature of CVD is vascular remodeling (VR), and the pathological changes are manifested by increased hypertrophy and stiffness of the arterial wall. The thickening of the arterial wall is mainly caused by the active proliferation of vascular smooth muscle cells (VSMCs). In this pathological process, the proliferation and migration of VSMCs are affected and regulated by many factors, such as vasoactive substances, growth factors, and extracellular matrix. Risk factors for CVD cause local inflammation in blood vessels. A large number of inflammatory factors can be released to damage vascular endothelial function, which leads to the synthesis and release of some cytokines, especially growth factors, acting on VSMC membrane receptors and activating intracellular signaling pathways[7, 8]. Eventually it leads to the expression of genes in the nucleus to promote the excessive proliferation of VSMCs and aggravate the pathological process of VR.
Angiotensin Ⅱ (Ang-Ⅱ) is a bioactive peptide produced by the renin-angiotensin-aldosterone system and acts on vascular smooth muscle. As an important active substance for regulating cardiovascular activity, it has a specific role in the occurrence of CVDs such as hypertension, myocardial hypertrophy, and heart failure. Existing studies have found that Ang-Ⅱ can induce VSMCs to release a large amount of inflammatory mediators, resulting in abnormal proliferation and formation of arterial plaques. As an initiator of the inflammatory response, interleukin-6 (IL-6) can induce B cells to differentiate and produce antibodies. In addition, it also induces T cell activation, proliferation, and differentiation, thereby participating in the body's immune response. Studies have shown that Chaihu-Shugan-San reduces the local inflammation of blood vessels by inhibiting the level of IL-6 in serum, thereby reducing the area of hyperplastic arterial plaque. Therefore, normalizing the body's inflammatory mediator levels may provide new insights for the prevention and treatment of vascular proliferative diseases. Intercellular cell adhesion molecule-1 (ICAM-1) as an important member of the immunoglobulin superfamily (IGSF) in adhesion molecules, is actively expressed in proliferating vascular endothelial cells. At the same time, it participates in physiological and pathological processes such as signal transduction and activation of cells, immune response, inflammatory response and angiogenesis. Vascular endothelial growth factor (VEGF) is the most critical factor in the process of angiogenesis. Studies have found that it mainly acts in the early stage of VR in combination with other growth factors to promote vascular hyperplasia greatly, thereby participating in the process of VR. More importantly, Studies have shown that VEGF and ICAM-1 are positively correlated with the degree of proliferation and migration of vascular cells, which can be used as indicators to judge abnormal proliferation of blood vessels[18, 19]. Transforming growth factor-β (TGF-β) can regulate the phenotypic transformation of VSMCs. It also affects the process of vascular wall remodeling by regulating the proliferation, migration and matrix deposition functions of VSMCs. Mammalian target of rapamycin (mTOR) is an important serine-threonine protein kinase downstream of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt). It can regulate the proliferation, survival, invasion and metastasis of tumor cells by activating ribosomal kinase. The study found that TGF-β, VEGF and PI3K/Akt/mTOR signaling pathways are closely related to cell proliferation and affect normal cardiovascular function[16, 20, 22]. Therefore, it is very important to deeply explore their related mechanisms. At present, the treatment methods for most CVDs are mainly divided into surgical intervention and drug intervention, but they all have certain side effects or problems of low patient compliance. Therefore, it is urgent to find a safe and effective medicine with low side effects.
Quyu Shengxin capsule (QSC) is the result of this subject starting from the theory of etiology and pathogenesis of traditional Chinese medicine, based on the experience of clinical practice, and combining modern medicine's understanding of CVD. It is made into hard capsules by the combination of astragalus, guizhi, trigonum, zedoary, tulipa, and zucchini. QSC has been used in the treatment of clinical blood stasis syndrome in China for many years. The blood stasis syndrome is closely related to the etiology of CVDs such as coronary heart disease, hypertension and atherosclerosis. The chemical markers of QSC include baicalin, astragaloside, cinnamaldehyde, curcumin, and brucine, which are reported to improve inflammation and abnormal cell proliferation[24–27]. A variety of active ingredients, including astragaloside, in its main component, astragalus (traditional Chinese medicine), have a certain effect on metabolic diseases such as diabetes and atherosclerosis[28, 29]. In recent years, the gene chip has become a new field of pharmacological research. It has been used to elucidate the interaction between multiple components and multiple pathways of active ingredients of Chinese herbal medicine. With the rapid development of bioinformatics and systems biology, more and more studies rely on gene chips to fully explore the potential mechanisms and potential targets of complex systems. Therefore, this study used gene chip detection to study the potential targets of QSC. To reveal whether QSC has an interventional treatment effect on CVDs such as abnormal vascular hyperplasia, the effect of QSC on inflammation and proliferation in VSMCs induced by Ang-II was studied, and the mechanism of related signaling pathways was further explored.