Recent advances in the pathophysiologic understanding of coronavirus disease 2019 (COVID-19) suggests that cytokine release syndrome (CRS) has an association with the severity of disease, which is characterized by increased tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-2, IL-7, and IL-10. Hence, managing CRS has been recommended for rescuing severe COVID-19 patients. TNF-α, one of the pro-inflammatory cytokines commonly upregulated in acute lung injury, triggers CRS and facilitates SARS-CoV-2 interaction with angiotensin-converting enzyme 2 (ACE2). TNF-α inhibitors, therefore, may serve as an effective therapeutic strategy for attenuating disease progression in severe SARS-CoV-2 infection. Below, we review the possibilities and challenges of targeting the TNF-α pathway in COVID-19 treatment.

Cardiovascular disease serves as the leading cause of death worldwide, with stenosis, occlusion, or severe dysfunction of blood vessels being its pathophysiological mechanism. Vascular replacement is the preferred surgical option for treating obstructed vascular structures. Due to the limited availability of healthy autologous vessels as well as the incidence of postoperative complications, there is an increasing demand for artificial blood vessels. From synthetic to natural, or a mixture of these components, numerous materials have been used to prepare artificial vascular grafts. Although synthetic grafts are more appropriate for use in medium to large-diameter vessels, they fail when replacing small-diameter vessels. Tissue-engineered vascular grafts are very likely to be an ideal alternative to autologous grafts in small-diameter vessels and are worthy of further investigation. However, a multitude of problems remain that must be resolved before they can be used in biomedical applications. Accordingly, this review attempts to describe these problems and provide a discussion of the generation of artificial blood vessels. In addition, we deliberate on current state-of-the-art technologies for creating artificial blood vessels, including advances in materials, fabrication techniques, various methods of surface modification, as well as preclinical and clinical applications. Furthermore, the evaluation of grafts both in vivo and in vitro, mechanical properties, challenges, and directions for further research are also discussed.

Cardiovascular diseases (CVDs) are still a major cause of global mortality and disability, seriously affecting people’s lives. Due to the severity and complexity of these diseases, it is important to find new regulatory mechanisms to treat CVDs. Ferroptosis is a new kind of regulatory cell death currently being investigated. Increasing evidence showed that ferroptosis plays an important role in CVDs, such as in ischemia/reperfusion injury, heart failure, cardiomyopathy, and atherosclerosis. Protecting against CVDs by targeting ferroptosis is a promising approach; therefore, in this review, we summarized the latest regulatory mechanism of ferroptosis and the current studies related to each CVD, followed by critical perspectives on the ferroptotic treatment of CVDs and the future direction of this intriguing biology.

For more than half a century, arteriovenous fistula (AVFs) has been recognized as a lifeline for patients requiring hemodialysis (HD). With its higher long-term patency rate and lower probability of complications, AVF is strongly recommended by guidelines in different areas as the first choice for vascular access for HD patients, and its proportion of application is gradually increasing. Despite technological improvements and advances in the standards of postoperative care, many deficiencies are still encountered in the use of AVF related to its high incidence of failure due to unsuccessful maturation to adequately support HD and the development of neointimal hyperplasia (NIH), which narrows the AVF lumen. AVF failure is linked to the activation and migration of vascular cells and the remodeling of the extracellular matrix, where complex interactions between cytokines, adhesion molecules, and inflammatory mediators lead to poor adaptive remodeling. Oxidative stress also plays a vital role in AVF failure, and a growing amount of data suggest a link between AVF failure and oxidative stress. In this review, we summarize the present understanding of the pathophysiology of AVF failure. Furthermore, we focus on the relation between oxidative stress and AVF dysfunction. Finally, we discuss potential therapies for addressing AVF failure based on targeting oxidative stress.

Restenosis is liable to occur following treatment with endovascular interventional therapy. Increasing evidence indicates that hydrogen sulfide (H2S) exhibits numerous physiological properties, including antioxidative and cardioprotective disease properties. Thus, the present study aimed to investigate the anti‑restenosis effects of H2S and its protective mechanisms. A balloon dilatation restenosis model was used, in which model Sprague‑Dawley rats were treated with sodium hydrosulfide (NaHS: A donor of H2S, 30 µmol/kg) by intraperitoneal injection for 4 weeks. Histological observations of the carotid artery were performed, and H2S production and the expression of Nuclear factor‑E2‑related factor 2 (Nrf2)/hypoxia‑inducible factor (HIF)‑1α signaling pathway proteins were measured. In addition, human umbilical vein endothelial cells (HUVECs) were treated with NaHS following the inhibition of Nrf2 or HIF‑1α expression. The expression of Nrf2/HIF‑1α signaling pathway proteins, tube formation and cell migration were evaluated thereafter. The results demonstrated that NaHS treatment significantly increased H2S production in rats with restenosis, and that neointimal thickness decreased significantly in arteries with restenosis. Furthermore, an increase in H2S production enhanced the nuclear accumulation of Nrf2 and expression of its downstream targets, heme oxygenase‑1 and superoxide dismutase, as well as HIF‑1α. Similar effects of NaHS on the expression of these proteins were observed in HUVECs. Additionally, these findings indicated that NaHS‑induced HIF‑1α expression was dependent on Nrf2 expression. NaHS treatment also markedly increased tube formation by upregulating vascular endothelial growth factor expression and cell migration, both of which were mediated by the Nrf2/HIF‑1α signaling pathway, and suppressed the migration and proliferation of human vascular smooth muscle cells. Thus, NaHS‑mediated H2S production was observed to prevent neointimal hyperplasia, promote activation of the Nrf2/HIF‑1α signal pathway, and enhance HUVEC tube formation and migration, thereby exerting protective effects on balloon injury‑induced restenosis.

Restenosis after angioplasty of peripheral arteries is a clinical problem involving oxidative stress. Hydrogen sulfide (H₂S) participates in oxidative stress regulation and activates nuclear factor erythroid 2-related factor 2 (Nrf2). This study investigated the effect of H₂S and Nrf2 on restenosis-induced arterial injury. Using an in vivo rat model of restenosis, we investigated whether H₂S inhibits restenosis after percutaneous transluminal angioplasty (PTA) and the oxidative stress-related mechanisms implicated therein. The involvement of Nrf2 was explored using Nrf2-shRNA. Neointimal formation and the deposition of elastic fibers were assessed histologically. Inflammatory cytokine secretion and the expression of proteins associated with oxidative stress and inflammation were evaluated. The artery of rats subjected to restenosis showed increased arterial intimal thickness, with prominent elastic fiber deposition. Sodium hydrosulfide (NaHS), an H₂S donor, counteracted these changes in vivo. Restenosis caused a decrease in anti-oxidative stress signaling. This phenomenon was inhibited by NaHS, but Nrf2-shRNA counteracted the effects of NaHS. In terms of inflammation, inflammatory cytokines were upregulated, whereas NaHS suppressed the induced inflammatory reaction. Similarly, Nrf2 downregulation blocked the effect of NaHS. In vitro studies using aortic endothelial and vascular smooth muscle cells isolated from experimental animals showed consistent results as those of in vivo studies, and the participation of the nuclear factor-kappa B signaling pathway was demonstrated. Collectively, H₂S played a role in regulating post-PTA restenosis by alleviating oxidative stress, modulating anti-oxidant defense, and targeting Nrf2-related pathways via nuclear factor-kappa B signaling.