Late coronary artery injury following chemoradiotherapy for thymic carcinoma: a case report.

INTRODUCTION: Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients' long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy. CASE PRESENTATION: The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components. CONCLUSIONS: Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.

Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis.

BACKGROUND: Studies have found that circular RNAs (circRNAs) play key roles in cardiovascular diseases. However, the function of circROBO2 in acute myocardial infarction (AMI) is unclear. This study aimed to investigate the pathogenesis of circROBO2 in AMI. METHODS: qRT-PCR and Western blot were used to determine the expression levels of circROBO2, miR-1184, and TRADD in AMI and sham-operated mouse models at mRNA and protein level, respectively. The relationship among miR-1184, circROBO2 and TRADD was evaluated by RNA immunoprecipitation (RIP) analysis and luciferase reporter gene analysis. The roles of circROBO2, miR-1184, and TRADD in myocardial cell apoptosis were evaluated using flow cytometry. Ultrasound echocardiography, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarction area, and myocardial cell apoptosis were measured to examine the effects of circROBO2 on myocardial injury. RESULTS: The expression levels of miR-1184 were significantly reduced, and the expression levels of circROBO2 and TRADD were significantly increased in MI group. CircROBO2 acted as a sponge for miR-1184 by upregulating the expression of TRADD. In addition, overexpression of miR-1184 enhanced the protective effect of knockdown of circROBO2 by partially inhibiting the expression of TRADD in vivo and in vitro. CONCLUSION: Knockdown of circROBO2 reduced the apoptosis of cardiomyocytes by increasing the expression levels of miR-1184, which in turn decreased the expression levels of TRADD in the myocardium post-MI.

NLRP3 inflammasome expression in peripheral blood monocytes of coronary heart disease patients and its modulation by rosuvastatin.

Nucleotide­binding oligomerization domain, leucine rich repeat, and pyrin domain­containing protein 3 (NLRP3) inflammasome has been implicated in a series of physiological and pathological processes. However, its correlation in coronary heart disease (CHD) still remains to be elucidated. The present study aimed to determine the expression of NLRP3 inflammasome in peripheral blood monocytes (PBMCs) of stable angina pectoris (SAP) and acute myocardial infarction (AMI) patients. In addition, the effect of rosuvastatin on their activities was analyzed in vitro. A total of 60 participants with SAP (n=20), AMI (n=20) and non­CHD controls (n=20) were enrolled. Fluorescence­activated cell sorting, real­time PCR, western blotting and enzyme­linked immunosorbent assay were performed to reveal the role of NLRP3 inflammasome. NLRP3 inflammasome was expressed in the PBMCs, and revealed an increased expression along the downstream interleukin (IL)­1ß and IL­18 in both SAP and AMI groups, compared to the control group. Moreover, there was a more marked increase in the expression of these indicators in AMI patients when compared to SAP patients. Interference with rosuvastatin in vitro revealed that the expression of NLRP3 inflammasome and its downstream cytokines were significantly downregulated in both SAP and AMI groups in a time­dependent manner. The activation of NLRP3 inflammasome may be involved in the development of CHD, and rosuvastatin could attenuate the inflammatory process of atherosclerosis by downregulating NLRP3 expression and its downstream mediators. These findings indicated a potential role of NLRP3 in the pathogenesis and management of CHD, and also provided new insights into the mechanistic framework of rosuvastatin activity.

[Expression of connexin 43 in peripheral blood monocytes from patients with acute coronary syndrome].

OBJECTIVE: To investigate the expression of connexin 43 (Cx43) in peripheral blood monocytes (PBMCs) from patients with acute coronary syndrome (ACS) and its clinical implications. METHODS: We prospectively collected the clinical data from 40 patients with ACS including 20 with unstable angina pectoris (UAP) and 20 with acute myocardial infarction (AMI) admitted in our department between January, 2018 and June, 2018, with 20 healthy subjects undergoing routine physical examinations serving as the control group. Peripheral blood samples were obtained from all the participants and plasma and PBMCs were separated. Enzyme-linked immunosorbent assay (ELISA) and turbidimetric inhibition immunoassay (TIIA) were used for analysis of plasma levels of interleukin (IL)-1ß and high sensitive C-reactive protein (hs-CRP), respectively; real-time quantitative RT-PCR and Western blotting were used to detect the mRNA and protein levels of Cx43 in the PBMCs. RESULTS: Compared with the control group, the patients with UAP showed significantly increased plasma levels of IL-1ß and hs-CRP (P < 0.001) and obviously elevated expressions of Cx43 at both mRNA and protein levels in the PBMCs (P < 0.001). Compared with the patients with UAP, the patients with AMI had significantly higher plasma IL-1ß and hs-CRP levels (P < 0.001 and P < 0.01) but lower expression levels of Cx43 in the PBMCs (P < 0.05). CONCLUSIONS: Patients with UAP and AMI have activated inflammatory responses and reverse changes in Cx43 expression in the PBMCs, suggesting the different roles of Cx43 in the pathogenic mechanisms of different types of ACS.

Effect of intra-coronary administration of tirofiban through aspiration catheter on patients over 60 years with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

The aim of this study was to compare the efficacy and safety of 2 approaches for intra-coronary administration of tirofiban (aspiration catheter versus guiding catheter) in patients over 60 years of age undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). It has been suggested that the administration of tirofiban by intra-coronary injection could promote drug absorption in the diseased region and enhance the inhibition of platelet aggregation, decreasing bleeding rates, but little is known about the comparative efficiency and safety of using guiding catheter versus aspiration catheter for delivery.Eighty-nine patients over 60 years of age with STEMI undergoing PCI were randomly divided into 2 groups according to the injection route for intracoronary administration of tirofiban [guiding catheter (n = 41) and aspiration catheter (n = 48)]. Baseline features, epicardial and myocardial perfusion, major adverse cardiac and cerebrovascular events (MACCEs), and bleeding rate were compared.No differences in age, gender, and history of hypertension, hypercholesterolemia, diabetes, and so on were observed (P > .05). The patients in the aspiration catheter group generally had a higher incidence of cerebral vascular disease. Compared with those in the guiding catheter group, patients in the aspiration catheter group obtained more favorable myocardial perfusion (P < .05). In-hospital and at 3-month and 6-month follow-ups, the MACCE rate and frequency of bleeding events were similar between the 2 groups (P > .05).Intra-coronary delivery of tirofiban through aspiration catheter led to better myocardial perfusion in STEMI patients over 60 years of age undergoing PCI compared with intra-coronary injection of tirofiban through guiding catheter. The 2 delivery routes were associated with similar rates of MACCEs and bleeding events.

[Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis].

OBJECTIVE: To explore the effects of simvastatin on vascular endothelial cell apoptosis and Bcl-2 protein expression in the aorta in a rat model of atherosclerosis. METHODS: Thirty-six rats were randomized into control group (n=10), atherosclerosis model group (n=13) and simvastatin intervention group (n=13). In the latter two groups, rat models of atherosclerosis were established by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6 weeks, and the control rats were fed with regular diet. In the intervention group, the rats were further fed with high-fat diet with daily simvastatin treatment for 4 weeks. After the treatments, the pathological changes and plaque in the thoracic aorta were observed, and the expression of Bcl-2 protein was detected with immunohistochemistry. TUNEL assay was used to determine the apoptosis index (AI) of the vascular endothelial cells. RESULTS: Compared with that in the control group, Bcl-2 protein expression in the aorta of atherosclerotic rats was significantly decreased (P<0.05); simvastatin treatment obviously increased the expression of Bcl-2 protein in atherosclerotic rats (P<0.05) to a level similar to that in the control group. The AI was the highest in the model group (P<0.05) and comparable between the control and simvastatin treatment group. CONCLUSION: The therapeutic effect of simvastatin against atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.

T-lymphocyte Kv1.3 channel activation triggers the NLRP3 inflammasome signaling pathway in hypertensive patients.

The aim of the current study was to investigate the correlation between voltage-gated potassium 1.3 (Kv1.3) channel of peripheral blood T-lymphocytes and the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in hypertensive patients. Peripheral blood samples from the hypertensive Kazakh patients (n=30) and healthy Kazakh subjects (n=30) were collected. The T lymphocytes and serum were separated, and the state of Kv1.3 channels was detected using the patch-clamp technique. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to detect the mRNA and protein expression levels of key molecules [NLRP3, caspase-1 and interleuking (IL)-ß] in the lymphocyte NLRP3 inflammasome pathway, while serum IL-1ß content was measured by ELISA assay. The results demonstrated no statistical difference in the subject baseline data between the two groups. While more significantly activated Kv1.3 channels were identified in the peripheral blood T-lymphocytes of the hypertension group compared to the normotension group, the mRNA and protein expression levels of NLRP3, caspase-1 and IL-1ß were elevated and their peripheral serum interleukin-1ß levels were significantly increased. After inhibiting the Kv1.3 channels using the classic potassium channel blocker, these indicators were all decreased significantly. The results indicate that the NLRP3 inflammasome pathway of peripheral blood T-lymphocytes in hypertensive Kazakh patients is activated, which may be correlated with the opening of the Kv1.3 channel.