A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases.

P2Y12 inhibitors, including aspirin, are key components of dual-antiplatelet therapy (DAPT), which is the optimal therapeutic strategy for preventing arterial thrombosis in patients with acute coronary syndromes (ACS) who underwent stent implantation. Ticagrelor is a cyclopentyl-triazole pyrimidine antiplatelet drug that was the first reversible oral P2Y12 receptor antagonist. Compared with clopidogrel, ticagrelor exerts a faster onset and offset of function by reversible and selective inhibition of platelet aggregation in ACS patients, including those with coronary artery blood revascularization. Despite improvement in stent materials, stent thrombosis (ST) due to high on-treatment platelet reactivity (HPR) to clopidogrel continues to occur. In addition to antiplatelet aggregation, ticagrelor displays pleiotropic cardioprotective effects, including improving coronary blood flow, reducing myocardial necrosis after an ischemic event, and anti-inflammatory effects. The benefits of ticagrelor over clopidogrel were consistent in the PLATO results, with lower incidence of the primary endpoint. Also, in 2020, the findings from the phase 3 THALES trial (NCT03354429) showed that aspirin combined with 90 mg of ticagrelor significantly reduced the rates of stroke and death compared with aspirin alone in patients with AIS or TIA. Here, we review recent research on the superiority of ticagrelor over clopidogrel, discuss the pharmacological mechanism, and present future perspectives. This review aims to present the roles of ticagrelor in the management of acute coronary syndrome, acute thrombotic disease, and other diseases.

Risk Factors of Ischemia Reperfusion Injury After PCI in Patients with Acute ST-Segment Elevation Myocardial Infarction and its Influence on Prognosis.

Purpose: To explore the risk factors of ischemia reperfusion injury (IRI) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and its influence on prognosis. Methods: The clinical data of 80 patients with STMEI undergoing PCI in our hospital from June 2020 to June 2021 were collected. According to whether IRI occurred after PCI, STMEI patients were divided into IRI group and non-IRI group. The basic information, clinical characteristics, examination parameters and other data of all patients were collected, and the prognosis of the two groups was observed. Risk factors were analyzed by fitting binary Logistic regression model. The survival prognosis was analyzed by Kaplan-Meier survival curve. Results: Logistic regression analysis showed that type 2 diabetes mellitus (T2DM), pre-hospital delay time (PHD) and door-to-balloon expansion time (DTB) were the influencing factors of IRI in patients with STMEI (p < 0.05). MACE occurred in 11 cases (32.35%) in the IRI group and 13 cases (28.26%) in the non-IRI group. Log-rank test showed p = 0.503, indicating no statistically significant difference. Conclusion: T2DM, PHD and DTB were the influencing factors of IRI in patients with STMEI, and IRI will not reduce the prognosis of patients.

Circ_0124644 enhances ox-LDL-induced cell damages in human umbilical vein endothelial cells through upregulating FOXO4 by sponging miR-370-3p.

BACKGROUND: Circular RNA circ_0124644 has crucial regulation in the progression of coronary artery diseases, including atherosclerosis (AS). The aim of this study was to explore the regulatory mechanism of circ_0124644 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury in human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability and proliferation were assessed using cell counting kit-8 (CCK-8) assay and EdU assay. The apoptosis detection was performed by flow cytometry. Angiogenesis was evaluated through tube formation assay. The protein analysis was conducted via western blot. Inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The expression determination of circ_0124644, microRNA-370-3p (miR-370-3p) and forkhead box protein O4 (FOXO4) was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to analyze the interaction between targets. RESULTS: Treatment of ox-LDL resulted in the inhibition of cell viability, proliferation and angiogenesis but the promotion of apoptosis and inflammation in HUVECs. These ox-LDL-induced cell damages were alleviated after the downregulation of circ_0124644. Circ_0124644 interacted with miR-370-3p, and the regulatory role of circ_0124644 was associated with the sponge function of miR-370-3p. Additionally, miR-370-3p targeted FOXO4 and circ_0124644 increased the expression of FOXO4 through acting as a sponge of miR-370-3p. Overexpression of miR-370-3p protected from ox-LDL-induced injury via the downregulation of FOXO4. CONCLUSION: All results revealed that circ_0124644 accelerated endothelial injury in ox-LDL-treated HUVECs by mediating miR-370-3p-related FOXO4 expression.

Reduced glutathione does not further reduce contrast-induced nephropathy in elderly patients with diabetes receiving percutaneous coronary intervention.

OBJECTIVE: To investigate the preventive effect of hydration combined with reduced glutathione on contrast-induced nephropathy (CIN) after coronary intervention therapy in elderly Chinese patients with diabetes. METHODS: Patients with diabetes aged ≥65 years, who received percutaneous coronary intervention (PCI) between 1 August 2016 and 31 December 2018, were enrolled and randomized into two groups: patients treated with hydration combined with reduced glutathione (treatment group) and patients who received hydration alone (controls). Serum creatinine and creatinine clearance levels were measured in all patients before PCI and then daily for 3 days after PCI. Occurrence of CIN (the primary endpoint) was defined as serum creatinine value 25% or 44.2 mmol/l (0.5 mg/dl) above baseline at 72 h after an exposure to contrast medium. RESULTS: A total of 396 patients were included (treatment group, n = 204; and controls, n = 192). The CIN occurrence rate in the treatment and control group was 5.88% and 6.77%, respectively, with no statistically significant between-group difference. CONCLUSION: In elderly patients with diabetes receiving PCI, the risk of CIN was not effectively lowered by hydration combined with reduced glutathione.

5-Hydroxytryptamine and Dopamine Neurons in the Cerebellum of the New-Hatching Yangtze Alligator Alligator sinensis.

Nissl and immunohistochemical staining methods were used to morphologically characterize the cerebellum of the new-hatching Yangtze alligator, and the cerebellar histological structure and the distribution profiles of 5-hydroxytryptamine (5-HT) and dopamine (DA) neurons were investigated for the first time. The results of cerebellar histological structure showed that there was a ventriculus cerebelli in the cerebellum of the new-hatching Yangtze alligator, the surface of the cerebellar cortex was not very smooth, the cerebellar cortex could be divided into four layers, which include external granular layer, molecular layer, Purkinje cell layer and granular layer, Purkinje cell layer could be characterized specially by multilayer, two cerebellar nuclei termed as the nucleus cerebelli lateralis and the nucleus cerebelli medialis were found in the cerebellar medulla. 5-hydroxytryptamine-immunoreactive (5-HT-IR) and dopamine-immunoreactive (DA-IR) neurons and fibers distributed widely in the cerebellum. The structures and profiles of 5-HT-IR and DA-IR neurons and fibers in the cerebellum of the Yangtze alligator were similar to that reported in other reptiles, but also had some specific features. The abundance of 5-HT and DA in cerebellum suggested that these highly conserved neurotransmitters would play important roles in motor control. Anat Rec, 302:861-868, 2019. © 2018 Wiley Periodicals, Inc.

Osthole protects against Ang II-induced endotheliocyte death by targeting NF-κB pathway and Keap-1/Nrf2 pathway.

Osthole, the main active constituents in traditional Chinese medicine fructus cnidii, has anti-inflammatory and anti-oxidant activities. Apoptosis of vascular endothelial cells is an important cause of cardiovascular disease. Inflammation and oxidative stress are two key factors in injury of endotheliocyte. In this study, we investigated the effect of osthole on Ang II-induced apoptosis of rat aortic endothelial cells (RAECs) and explored the underlying mechanisms. In the present study, the protective effects of osthole on RAECs induced by Ang II in vitro were tested. Additionally, molecular docking and molecular dynamics (MD) simulations were utilized to investigate the potential binding mode of osthole to NF-κB and Keap1. Our results showed osthole remarkably attenuates Ang II-induced apoptosis of RAECs via alleviating inflammation and oxidative stress. Molecular docking and MD simulations revealed the potential interaction of osthole bind to the P65 subunit of NF-κB and the Keap1 protein, an adaptor for the degradation of Nrf2. We further found that osthole decreased Ang II-induced inflammation and oxidative stress through respectively modulating NF-κB and Nrf2 pathways in RAECs. These studies provide evidence that osthole may represent a potential therapeutic agent for the treatment of vascular injury.