[Effects of hot shock protein 70 inhibitor PFTµ on inflammatory response in lipopolysaccharide-stimulated RAW264.7 cells and mice underwent myocardial ischemia-reperfusion injury].

OBJECTIVE: To observe the effects of hot shock protein 70 (HSP70) inhibitor (PFTµ) on inflammation response in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice underwent myocardial ischemia-reperfusion (I/R) injury. METHODS: RAW264.7 macrophage line of mice was stimulated by LPS as an inflammatory model. These were divided into control (15 min DMSO pretreatment and LPS 2 g/L) and PFTµ treated groups (15 min PFTµ 20 µmol/L pretreatment and LPS 2 g/L). NO concentration was measured by Griess Kit. The expression of iNOS protein and mRNA were detected by Western blot and RT-PCR. Infarct size was determined on mice underwent myocardial ischemia-reperfusion (I/R) injury in the absence or presence (PFTµ 40 mg/kg, intraperitoneal injection). RESULTS: PFTµ significantly blocked the production of NO and protein and mRNA expression of iNOS (P < 0.05 vs. control). PFTµ also significantly reduced the infarct size on mice underwent I/R injury (P < 0.05 vs. control). CONCLUSION: These results suggest that PFTµ could be a potential therapeutic agent for the treatment of inflammatory diseases through inhibiting the production of NO and reducing inflammatory responses.

[The protective role of transient receptor potential vanilloid subtype 1 in post-myocardial infarction inflammation process.].

OBJECTIVE: To investigate the protective role of transient receptor potential vanilloid subtype 1 (TRPV1) in inflammatory process after myocardial infarction. METHODS: The survival rate, infarct size, the levels of plasma cardiac troponin I, infiltration of inflammatory cells, the levels of cytokines and chemokines, and cardiac function were monitored 3 and 7 days post-myocardial infarction in TRPV1 gene knockout (TRPV1(-/-)) and wild type (WT) mice. RESULTS: The survival rate was significantly lower in TRPV1(-/-) mice than that in WT mice (62.5% vs. 82.1%, P < 0.05). The infarct size on day 3 after MI was significantly larger in TRPV1(-/-) mice than that in WT mice (INF/AAR: 69.5% +/- 3.1% vs. 40.1% +/- 2.6%, P < 0.05). Plasma cardiac troponin I level, number of infiltrated inflammatory cells including neutrophils and macrophages were significant increased in TRPV1(-/-) mice compared to WT mice. Expressions of cytokines including TNF-alpha, IL-1beta, and IL-6, chemokines including MCP-1 and MIP-2 in the infarct area at 3 and 7 days after MI were significantly higher in TRPV1(-/-) mice than those in WT mice (all P < 0.05). Furthermore, end-systolic and -diastolic diameters were significantly increased and contractile function of the heart significantly reduced in TRPV1(-/-) mice compared to WT mice. CONCLUSION: TRPV1 gene deletion results in reduced survival rate, excessive inflammation, deteriorated cardiac function and aggravated left ventricular remodelling after MI, indicating that TRPV1 may prevent infarct expansion and cardiac injury by inhibiting inflammation and reservation cardiac function.

Combination of C-reactive protein and cardiac troponin I for predicting adverse cardiac events after sirolimus-eluting stent implantation.

AIMS: We assessed the predictive value of a combination of C-reactive protein (CRP) and cardiac troponin I (cTnI) in a 2-year prospective study in patients undergoing sirolimus-eluting stents (SES) implantation. METHODS AND RESULTS: CRP and cTnI levels were examined 1 day before and after SES implantation in 322 patients. CRP level greater than 3.0 mg/l (defining the high serum CRP levels) and cTnI level greater than 1.0 microg/l (defining the high serum cTnI levels) were considered abnormal. Major adverse cardiac events were defined as nonfatal myocardial infarction (MI), target vessel revascularization (TVR), and cardiac death. After 2+/-0.2 years of follow-up, there were 11 MI, 19 TVR, and 11 cardiac deaths. After adjustment for relevant risk factors, the combination of high CRP and cTnI remained predictive of adverse cardiac events, with the presence of both elevated CRP and cTnI associated with the highest risks of MI [relative risk (RR): 4.0, 95% confidence interval (CI): 2.3-6.4], TVR (RR: 3.3, 95% CI: 2.8-5.3), and cardiac death (RR: 4.2, 95% CI: 2.6-6.0). The presence of either a high CRP or cTnI was associated with an intermediated risk of MI (RR: 1.7, 95% CI: 1.2-2.2), TVR (RR: 1.5, 95% CI: 1.2-2.7), and cardiac death (RR: 2.8, 95% CI: 2.2-3.6). CONCLUSION: The combination of elevated CRP and cTnI increased the risk of adverse cardiac events, demonstrating the additive impacts of active inflammation and myocardial injury on prognosis after SES implantation.

[Elevated serum high sensitivity C-reactive protein and endothelial dysfunction in silent myocardial ischemia].

OBJECTIVE: To explore the association between silent myocardial ischemia (SMI) and high sensitivity C-reactive protein (hsCRP) and endothelial dysfunction. METHODS: 148 asymptomatic patients (103 men and 45 women) with known CAD were recruited. According to the results of ambulatory electrocardiography recording (AECG), patients were divided into two groups: SMI group and non-SMI group. All the patients underwent assessment of endothelial dependent flow mediated dilation (FMD) with high resolution ultrasound for the evaluation of endothelial function and 24-hour three-lead ambulatory electrocardiography recording for the detection of SMI. Serum hsCRP, blood glucose, HDL cholesterol, LDL cholesterol and triglycerides were measured. RESULTS: Sixty of the 148 patients had SMI, with a relatively high prevalence of 40.5%. The serum concentration of hsCRP in SMI group was higher than that in non-SMI group (1.86 +/- 0.52 vs 0.91 +/- 0.36, P < 0.05) and FMD was lower in SMI group than that in non-SMI group (3.02 +/- 1.46 vs 6.36 +/- 3.79, P < 0.05). In logistic regression analysis, SMI was found to be related only to FMD (beta = -0.452, P = 0.046, OR = 1.572) and hsCRP (beta = 1.233, P = 0.036, OR = 1.632). CONCLUSIONS: SMI shows a relatively high prevalence in patients with known stable CAD; it is suggested that this population still needs to be carefully evaluated with risk stratification. SMI may be caused by inflammation and endothelial dysfunction. FMD and hsCRP may serve as the surrogate markers in screening SMI in patients with known CAD.