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BACKGROUND: Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma (HCC). In recent years, several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). AIM: To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC. METHODS: All eligible cohort, non-randomized controlled, and randomized controlled trial studies from the PubMed, Web of Science, Embase, Cochrane Library, and MedLine databases up to March 20, 2024 were screened for the present meta-analysis. The study endpoints included complete response (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Stata 16/18 software was used for this meta-analysis, and a P value of <0.05 was considered statistically significant. RESULTS: A total of 29 studies with 1754 patients were included. Among the patients who received the TACE therapy with TKIs and ICIs, the tumor response results revealed a pooled CR, ORR, and DCR of 14% [95%CI (0.11-0.18)], 61% [95%CI (0.55-0.66)], and 85% [95%CI (0.83-0.87)], respectively. In terms of the survival outcomes, the pooled median PFS and OS were 10.25 months [95%CI (9.31-11.18)] and 20.47 months [95%CI (18.98-21.97)], respectively. The pooled prevalence of all-grade AEs during the triple treatment was 90% [95%CI (0.84-0.94)] and that of grade ≥ 3 AEs was 32% [95%CI (0.24-0.42)]. CONCLUSION: The combination therapy of TACE, TKIs, and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a lethal malignancy due to its heterogeneity and aggressive behavior. Recently, somatic mutations and tumor cell interactions with the surrounding tumor immune microenvironment (TIME) have been reported to participate in HCC carcinogenesis and predict HCC progression. In this study, we aimed to investigate the association between tumor mutational burden (TMB) and TIME in HCC. Additionally, we sought to identify differentially expressed genes (DEGs) associated with HCC prognosis and progression. METHODS: The expression, clinical, and mutational data were downloaded from the cancer genome atlas (TCGA) database. The immune infiltration levels and TMB levels of the HCC samples were estimated and the samples were divided into immune cluster (ICR)-1 and 2 based on immune infiltration score and high and low TMB groups based on TMB score. Thereafter, differential gene expression analysis was conducted to identify the DEGs in the ICR1/2 and high/low TMB groups, and the intersecting DEGs were selected. Thereafter, Cox regression analysis was performed on 89 significant DEGs, among which 19 were associated with prognosis. These 19 DEGs were then used to construct a prognostic model based on their expression levels and regression coefficients. Thereafter, we analyzed the DEGs in mutant and wildtype TP53 HCC samples and identified high BCL10 and TRAF3 expression in the mutant TP53 samples. BCL10 and TRAF3 expression was detected by real-time quantitative reverse transcription PCR and immunohistochemistry, and their clinical correlation, biological function, and immune infiltration levels were analyzed by chi-square analyses, Gene Set Enrichment Analysis (GSEA), and "ssGSEA", respectively. RESULTS: The results of our study revealed that immune infiltration level was correlated with TMB and that they synergistically predicted poor prognosis of HCC patients. DEGs enriched in immune-related pathways could serve as indicators of immunotherapy response in HCC. Among these DEGs, BCL10 and TRAF3 were highly expressed in HCC tissues, especially in the mutant TP53 group, and they co-operatively exhibited immunological function, thereby affecting HCC progression and prognosis. CONCLUSION: In this study, we identified BCL10 and TRAF3 as potential prognostic indicators in HCC patients. Additionally, we found that BCL10 and TRAF3 influence TMB and TIME in HCC patients and can be used for the development of immune-based therapies for improving the long-term survival of HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Mutação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Humanos , Microambiente Tumoral/imunologia , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genéticaRESUMO
BACKGROUND: The role of methylcrotonoyl-CoA carboxylase 2 (MCCC2) in the development of tumors is well-established, and the involvement of leucine in the liver is well-known. However, the role of MCCC2 and the correlation between MCCC2 and leucine in the progression of hepatocellular carcinoma (HCC) have not yet been reported. METHODS: In this study, the Gepia database was used to evaluate the prognostic value of MCCC2 in HCC. The expression and localization of MCCC2 in HCC cells were determined by western blot and immunofluorescence assays. Flow cytometry and CCK-8 and transwell assays were carried out to explore the effect of MCCC2 on cell proliferation, migration, and invasion. In addition, mass spectrometry analysis was used to predict the potential cell function of MCCC2 in HCC. RESULTS: We found that the expression of MCCC2 increased in HCC tissues and that high expression of MCCC2 could predict poor outcomes in HCC patients. Knockdown expression of MCCC2 in HCC cells could reduce cell proliferation, migration, and invasion ability in vitro and could inhibit HCC cell proliferation in vivo. Interestingly, we found that HCC cells transfected with MCCC2-sgRNA failed to respond to leucine deprivation. Meanwhile, leucine deprivation inhibited cell proliferation, migration, and invasion in HCC cells where MCCC2 was present rather than in cells where MCCC2 was absent. In addition, knockdown of MCCC2 significantly reduced the glycolysis markers, glucose consumption, lactate secretion, and acetyl-CoA level, which is a product of leucine metabolism. Furthermore, we found that MCCC2 promotes the activation of ERK. Profiling the MCCC2 binding proteins revealed that MCCC2-associated proteins are enriched in biological processes, such as protein metabolism, energy pathway, and metabolism in HCC cells. CONCLUSIONS: Our findings revealed that MCCC2 plays a critical role in the development of HCC, and the leucine metabolism pathway might be a novel target in HCC treatment.
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AIM: To elucidate whether the interaction between Anxa2 and Stat3 could promote the progression of hepatocellular carcinoma (HCC) and that high co-expression of Anxa2 and Stat3 could predict poor prognosis in HCC patients. METHODS: We investigated Anxa2 and Stat3 expression using Western blot analysis in 4 HCC and adjacent nontumor tissues and using immunohistochemistry in 100 patients' paraffin sections. Then we assessed the expression of Stat3, Anxa2 and co-expression of Stat3 and Anxa2 with relevant clinical pathological parameters and their prognostic value in HCC patients. The recurrence and overall survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models. RESULTS: The incidence of high Stat3 expression in HCC tissues (35%) was significantly higher than that in non-HCC tissues (8%) (P < 0.001). The same result was observed in Anxa2 (P < 0.001). Also, the overexpression of Stat3 or Anxa2 showed a significant relationship with the recurrence of the 100 HCC patients (P = 0.012; P = 0.003). Additionally, tumor size >3 cm in diameter, multiple tumor number, and the presence of microvascular tumor thrombus were also significantly associated with recurrence in 100 patients. Then, all enrolled patients were divided into four groups according to IHC score of Stat3 and Anxa2, and the results indicated a significant difference in recurrence time between the subgroups (P < 0.001). What's more, co-highexpression of Stat3 and Anxa2 was related to the presence of microvascular tumor thrombus (P = 0.003) and poor tumor differentiation (P < 0.001), but not relevant with other clinical features (All P > 0.05). CONCLUSION: The expression of Stat3, Anxa2, or co-high-expression of the two proteins was associated with HCC recurrence and survival.
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Anexina A2/biossíntese , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator de Transcrição STAT3/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
Objective To invesgate the safety and efficacy of the second generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) stent in diabetic patients by a subgroup analysis of of the CREDITⅡand CREDIT Ⅲ trials. Methods All patients who were implanted with the EXCEL2 stent were enrolled in the CREDITⅡand CREDIT Ⅲ trials. The primary endpoint was target lesion failure at 24-month, defi ned as a composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization(TLR). The secondary endpoint was endpoints including all-cause death, all myocardial infarction (MI) or any revascularization.Results A total of 828 patients were included from the patients who were implanted with the EXCEL2 stent in the CREDIT II and CREDIT Ⅲ trials. 24-month follow-up rate was 99.5%. There was no significant difference in the primary endpoint (P>0.05) and event rates of the secondary endpoints(P>0.05) between the diabetic and non-diabetic group, which included all-cause death[diabetics (2.5%)vs.non-diabetics(1.4%),P>0.05],myocardial infarction(MI)(7.5% vs.5.0%,P>0.05),all from of revascularization(5.0% vs.3.9%,P>0.05),and stent thrombosis(0.6% vs.0.4%,P>0.05).Conclusions EXCEL 2 stent met the objective performance goal on effcacy and safety, which can reduce make stent restenosis, target vessel revascularization ,with 160 diabetic cases among them, and stent thrombosis in diabetic patients.
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<p><b>BACKGROUND</b>In cardiology, it is controversial whether different therapy strategies influence prognosis after acute coronary syndrome. We examined and compared the long-term outcomes of invasive and conservative strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and characterized the patients selected for an invasive approach.</p><p><b>METHODS</b>A total of 976 patients with acute NSTEMI were collected from December 2006 to October 2012 in the First Affiliated Hospital of Dalian Medical University Hospital. They are divided into conservative strategy (586 patients) and invasive strategy (390 patients) group. Unified follow-up questionnaire was performed by telephone contact (cut-off date was November, 2013). The long-term clinical events were analyzed and related to the different treatment strategies.</p><p><b>RESULTS</b>The median follow-up time was 29 months. Mortality was 28.7% (n = 168) in the conservative group and 2.1% (n = 8) in the invasive management at long-term clinical follow-up. The secondary endpoint (the composite endpoint) was 59.0% (n = 346) in the conservative group and 30.3% (n = 118) in the invasive management. Multivariate analysis showed that patients in the conservative group had higher all-cause mortality rates than those who had the invasive management (adjusted risk ratio [RR] = 7.795; 95% confidence interval [CI]: 3.796-16.006, P < 0.001), and the similar result was also seen in the secondary endpoint (adjusted RR = 2.102; 95% CI: 1.694-2.610, P < 0.001). In the subgroup analysis according to each Thrombolysis in Myocardial Infarction risk score (TRS), log-rank analysis showed lower mortality and secondary endpoint rates in the invasive group with the intermediate and high-risk patients (TRS 3-7).</p><p><b>CONCLUSIONS</b>An invasive strategy could improve long-term outcomes for NSTEMI patients, especially for intermediate and high-risk ones (TRS 3-7).</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda , Mortalidade , Patologia , Terapêutica , Infarto do Miocárdio , Mortalidade , Patologia , Terapêutica , Prognóstico , Estudos RetrospectivosRESUMO
<p><b>BACKGROUND</b>Females with acute myocardial infarction (AMI) have a higher risk of adverse outcomes because of receiving less evidence-based medical care. Our aim was to investigate the gender disparity in early death after ST-elevation myocardial infarction (STEMI) in the current era.</p><p><b>METHODS</b>A total of 1429 consecutive patients with STEMI in the Liaoning district were analyzed. We compared hospital care and cardiac event data by sex for in-patients with acute STEMI within 24 hours of symptom onset.</p><p><b>RESULTS</b>In the emergency reperfusion group (n = 754), in-hospital mortality occurred in 4.2% of the males and 11.2% of the females (P = 0.001). In the non-emergency reperfusion group (n = 675), in-hospital mortality occurred in 13.0% of the males and 22.9% of the females (P = 0.001). Multivariate Logistic regression analysis revealed female sex as an independent risk factor of death for STEMI patients during hospitalization (OR = 1.691, P = 0.007). After controlling for patients who died within 24 hr after admission, female sex was no longer an independent risk factor (OR = 1.409, P = 0.259).</p><p><b>CONCLUSION</b>Female sex was an independent risk factor for in-hospital mortality of STEMI patients, which is explained by an excess of very early deaths.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angioplastia Coronária com Balão , Mortalidade Hospitalar , Infarto do Miocárdio , Mortalidade , Terapêutica , Fatores de Risco , Fatores SexuaisRESUMO
Objective To investigate and analyze the impact of gender difference on outcome and prognosis of ST-segment elevation myocardial infarction (STEMI) in patients treated with primary percutaneous coronary intervention (PCI).Methods This was a prospective and multicentered observation study.All the patients with acute STEMI admitted to the hospitals from June 1st 2009 to June 1st 2010 were continuously recruited.In this study,a unified questionnaire was applied and the 382 patients satisfied the criteria.A unified follow-up questionnaire was used on patients who were discharged from the hospital.Results On average,the female patients were 8 years older than the males.The median “symptom-to-balloon time” was 312.5 minutes in females and 270.0 minutes in males,and it was significantly different (P=0.007).During hospitalization,a higher proportion of female patients developed heart failure,angina and bleeding.No gender differences were found on the in-hospital mortality rates and medical therapy recommended by the guideline.The female patients were more prone to multi-vessel disease than males (P=0.002).Success rates of primary PCI did not show any gender differences.One-month mortality and other cardiovascular events also did not show gender difference when the patients were followed for one month after being discharged.The rates of heart failure and re-hospitalization due to cardiac incidents among female patients were obviously higher than the males,three months after being discharged (P=0.007,respectively).However,the three-month and long-term cardiac mortality did not show differences related to gender.Female patients were associated with higher all-cause mortality than that in males,but there was no statistically significant difference (female 4.2% vs.male 1.6%;P=0.056).Data from multi-factor regression analysis showed that being female was not an independent predictor related to in-hospital mortality or during the follow-up period.Conclusion Being female was not an independent predictor of in-hospital mortality or during follow-up period among patients who were treated with primary PCI.Worse long-term outcome seen in female patients was likely to be explained by older age or longer pre-hospital delayed time.
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<p><b>BACKGROUND</b>In cardiology, it is controversial whether gender influences prognosis after acute myocardial infarction (MI). We examined the 30-day and 1-year prognosis for female patients with ST-elevation myocardial infarction (STEMI) in Liaoning province, and we analyzed factors that influenced these outcomes.</p><p><b>METHODS</b>This was a prospective, multicenter, observational study in which patient data were collected by questionnaire at the time of diagnosis and at approximately 30 days and 1 year later by telephone inquiries. Patients were diagnosed with STEMI between June 1, 2009 and June 1, 2010 at any of the 20 hospitals that gave treatment representative of current STEMI treatment in Liaoning Province. Unified follow-up questionnaire was used to visit the STEMI patients.</p><p><b>RESULTS</b>We analyzed data from a total of 1429 consecutive patients with STEMI in Liaoning province. Female patients were older (70.0 vs. 60.3, P < 0.001) and were less likely to receive emergency reperfusion therapy than male ones (39.2% vs. 58.0%, P < 0.001). Female gender was associated with higher unadjusted 30-day mortality rates (HR = 2.118, 95%CI: 1.572 - 2.854, P < 0.001) and higher unadjusted 1-year mortality rates (HR = 2.174, 95%CI: 1.659 - 2.848, P < 0.001). Multivariate Cox regression analysis showed that female gender was not an independent predictor of 30-day mortality rates (HR = 1.273, 95%CI: 0.929 - 1.745, P = 0.133) nor of 1-year mortality rates (HR = 1.112, 95%CI: 0.831 - 1.487, P = 0.475).</p><p><b>CONCLUSIONS</b>Women with STEMI appear to be at increased risk of 30-day and 1-year mortality compared with male STEMI patients, but this difference may be explained by older age and less frequent receipt of reperfusion therapy among the women.</p>
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China , Infarto do Miocárdio , Mortalidade , Cirurgia Geral , Reperfusão Miocárdica , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
This case report we presented aims to report a-31-year-old man with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) who developed myocardial infarction (MI) and also aims to discuss the possible mechanisms. The results showed that traditional risk factors alone do not cause coronary heart disease with SLE, and SLE-related factors influence the atherogenic process. We found that although SLE patients with acute MI benefit from percutaneous coronary intervention (PCI) therapy, it is very important to choose the reasonable antithrombotic strategies in patients with SLE and APS undergoing PCI who require oral anticoagulant therapy.
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Adulto , Humanos , Masculino , Angioplastia Coronária com Balão , Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Infarto do Miocárdio , TerapêuticaRESUMO
<p><b>BACKGROUND</b>Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1β.</p><p><b>METHODS</b>Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1β (5 µg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>QCA showed severe stenosis in IL-1β treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 ± 0.06) mm vs. (0.33 ± 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 ± 1.7) mm(2), PES (27.2 ± 1.6) mm(2) vs. BMS (76.2 ± 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 ± 0.03, PES 0.48 ± 0.49 vs. BMS 0.58 ± 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 ± 0.08 vs. PES 0.65 ± 0.13, BMS 0.70 ± 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS.</p><p><b>CONCLUSION</b>SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.</p>
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Animais , Masculino , Angioplastia Coronária com Balão , Reestenose Coronária , Stents Farmacológicos , Inflamação , Interleucina-1beta , Farmacologia , Paclitaxel , Sirolimo , SuínosRESUMO
<p><b>OBJECTIVE</b>To evaluate the value and limitations of multislice spiral CT in diagnosing coronary artery stenoses.</p><p><b>METHODS</b>A total of 65 patients with known or suspected coronary artery disease were examined by multislice spiral CT (retrospectively ECG-gating; 0.5 s rotation; one-sector reconstruction algorithm; intravenous contrast agent) and the results were compared with quantitative coronary angiography.</p><p><b>RESULTS</b>In the 889 coronary artery segments of 65 patients, 795 could be evaluated by CT (89.4%), 148 out of 167 coronary artery segments with significant stenoses (> or = 50% reduction of vessel diameter) were correctly detected by CT, 597 out of 628 coronary artery segments with normal or mild stenosis (< 50% reduction of vessel diameter) were correctly detected by CT. These values correspond to a sensitivity of 88.6%, specificity of 95.1%, positive predictive value of 82.7%, and negative predictive value of 96.9% for the detection of significant coronary artery stenosis by CT. Adding the 23 coronary artery segments with significant stenosis which could not be judged by CT, the sensitivity of CT for diagnosing coronary stenosis was 77.9%. In the 795 evaluable coronary artery segments, 78 out of 86 coronary artery segments with high-grade stenosis (> or = 75% reduction of vessel diameter) were correctly detected by CT, 692 of 709 coronary artery segments with normal or mild stenosed (< 75% reduction of vessel diameter) were correctly detected by CT. These values correspond to a sensitivity of 90.7%, specificity of 97.6%, positive predictive value of 82.1%, and negative predictive value of 98.9% for the detection of high-grade coronary artery segments stenosis by CT. Adding 13 coronary artery segments with high-grade stenosis which could not be judged by CT, the sensitivity was 78.8%.</p><p><b>CONCLUSION</b>Multislice spiral CT permits the visualization of significant coronary artery stenosis with high accuracy in case of sufficient image quality.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Coronária , Métodos , Estenose Coronária , Diagnóstico , Diagnóstico por Imagem , Eletrocardiografia , Valor Preditivo dos Testes , Tomografia Computadorizada Espiral , MétodosRESUMO
<p><b>OBJECTIVE</b>To observe the effects of rapamycin on the expressions of Rho-kinase and p27 mRNA during vascular intimal proliferation in a porcine model of coronary stenosis induced by interleukin-1beta (IL-1beta).</p><p><b>METHODS</b>The proximal segments of LAD and LCX were wrapped with cotton mesh that had absorbed sepharose bead solution with or without IL-1beta. Selective coronary angiography was performed two weeks later and the animals were killed for collecting the samples for histopathology and RT-PCR analyzing of Rho-kinase and p27 mRNA.</p><p><b>RESULTS</b>The expressions of Rho-kinase and p27 mRNA could be visualized in normal coronary wall. The expression of Rho-kinase mRNA was significantly enhanced and the expression of p27 mRNA was significantly decreased during the process of intimal proliferation induced by IL-1beta. Rapamycin significantly inhibited the intimal proliferation, reduced the infiltration of inflammatory cells, reduced the expression of Rho-kinase mRNA and increased the expression of p27 mRNA.</p><p><b>CONCLUSIONS</b>The expression of Rho-kinase mRNA is upregulated and p27 mRNA downregulated in coronary artery stenosis induced by IL-1beta and these effects could be abolished by cotreatment with rapamycin.</p>
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Animais , Masculino , Angiografia Coronária , Vasos Coronários , Metabolismo , Patologia , Modelos Animais de Doenças , Interleucina-1beta , Farmacologia , RNA Mensageiro , Metabolismo , Sirolimo , Farmacologia , Suínos , Túnica Íntima , Metabolismo , Patologia , Quinases Associadas a rho , MetabolismoRESUMO
<p><b>OBJECTIVE</b>Phosphorylation of myosin light chain (MLC) is one of the most important steps for vascular smooth muscle contraction and Rho-kinase is involved in this process. We investigated the role of Rho-kinase in a porcine coronary artery spasm model with interleukin-1beta.</p><p><b>METHODS</b>Segments of left coronary artery adventitia were surrounded by normal saline (n = 8) or IL-1beta agarose microne (n = 8) for 2 weeks. Vasospastic responses to intracoronary serotonin or histamine then studied at the saline or IL-1beta-treated site. The Rho-kinase mRNA expression in the treated site was measured by reverse transcription-polymerase chain reaction analysis (RT-PCR). The extent of phosphorylation of myosin-binding subunit of myosin phosphates (MBS, one of the major substrates of Rho-kinase) were quantified by Western blot analysis.</p><p><b>RESULTS</b>Intracoronary serotonin or histamine repeatedly induced coronary artery spasm and coronary arterial stenosis was evidenced at IL-1beta-treated site. Expression of Rho-kinase mRNA in IL-1beta-treated site was significantly increased compared to saline treated site (98.20% +/- 7.66% vs. 63.70% +/- 4.26%, P < 0.05). Western blot analysis showed that during the serotonin-induced contractions the extent of phosphorylation of MBS was also significantly increased in the spastic site (25,485 +/- 4745 vs. 6510 +/- 779, P < 0.05).</p><p><b>CONCLUSION</b>Rho-kinase upregulation at the spastic site and increased phosphorylation of myosin-binding subunit of myosin phosphates are key players in inducing vascular smooth muscle hypercontraction in this porcine model.</p>