Protective effect of HSP27 in atherosclerosis and coronary heart disease by inhibiting reactive oxygen species.

OBJECTIVE: To clarify the mechanism of heat shock protein 27 (HSP27) as a diagnostic biomarker in coronary heart disease (CHD) and atherosclerosis (AS). METHOD: Expressions of HSP27 in patients with CHD and healthy controls were determined by enzyme-linked immunosorbent assay and the expressions of HSP27 in aortas of patients with CHD and healthy controls were measured by immunohistochemistry. Receiver operating characteristic curve was applied to assess the diagnostic performance of HSP27 in CHD. ApoE-/- mice were included and accordingly grouped. The expressions of HSP27 in AS plaque were measured by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. AS plaque was observed using hematoxylin and eosin staining. DHE was used to detect reactive oxygen species (ROS) levels in aortas. The expressions of mitochondrial apoptosis-related proteins were measured by Western blot analysis. Cell apoptosis was determined by TUNEL staining. RESULTS: HSP27 was highly expressed in patients with CHD than in healthy controls ( P < 0.01). In comparison to the normal group, the model group had increased the relative positive area of HSP27 and higher expressions of HSP27, Bax, caspase-3, and apoptosis index (AI) but decreased Bcl-2 expression in AS plaque, as well as larger plaque areas and elevated ROS levels in the aorta (all P < 0.05). The HSP27-small interfering RNA group had increased expressions of Bax, caspase-3, and AI but decreased Bcl-2 and HSP27 expressions in AS plaque, as well as larger plaque areas, the relative positive area of HSP27 and higher ROS levels in aorta when compared with those in the model group (all P < 0.05). CONCLUSION: HSP27 exerts its protective role by suppressing ROS and AS progression by inhibiting mitochondria apoptosis pathway in CHD.

[High maintenance dose of clopidogrel improves long-term clinical outcomes in patients with elective percutaneous coronary intervention].

OBJECTIVE: To evaluate the efficacy of a 300 mg loading dose of clopidogrel followed by 150 mg as maintenance dose in patients with percutaneous coronary intervention (PCI). METHODS: A total of 108 consecutive patients undergoing elective PCI were recruited from our hospital from July 2007 to July 2008. A 300 mg loading dose was administered prior to PCI. Then they were randomized to receive clopidogrel 75 mg (n = 55) or 150 mg (n = 46) daily for 30 days. From Day 30 to Month 6 post-operation, all of them received 75 mg/d clopidogrel and were followed up for a mean period of 6 months. RESULTS: Thirty days after PCI, the platelet inhibition of the 150 mg group was significantly higher than the 75 mg group (64.2% ± 13.3% vs 52.6% ± 14.3%, P = 0.00). The ratios of fatal or non-fatal myocardial infarction (MI) (1(1.8%) vs 3 (6.5%), P = 0.405) and target vessel revascularization (TVR) (4(7.2%) vs 6 (13.0%), P = 0.714) were significantly lower in the 150 mg group than those in the 75 mg group. So the overall incidence of MACE including death, MI and TVR was obviously lower in the 150 mg group than that in the 75 mg group (13.0% vs 20.2%, absolute risk reduction 7.3%). CONCLUSION: A high clopidogrel maintenance dose of 150 mg daily for the first month after PCI reduces the risk of long-term adverse events in patients with elective percutaneous coronary intervention.

[Effect of tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To observe the effect of glycoprotein receptor blockade tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention (PCI). METHODS: From April 2006 to April 2008, 157 acute anterior myocardial infarction patients without ST segment resolution after PCI were randomly allocated to tirofiban (intravenous bolus 10 microg/kg followed by intravenous infusion of 0.15 microgxkg(-1)xmin(-1) for 48 h, n = 80) or equal volume saline (control group, n = 77). Baseline characteristics, PCI features and clinical outcomes during hospitalization, left ventricular ejection fractions (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at 30 and 180 days after discharge were compared between the two groups. RESULTS: The baseline clinical characteristics were comparable between the two groups. Compared to control group, the MACE rates and re-infarction rates at 30 days (6.3% vs.18.2%, P < 0.05; 1.3% vs.9.1%, P < 0.05, respectively) and 180 days (10.0% vs.23.4%, P < 0.05; 2.5% vs.10.4%, P < 0.05, respectively) were significantly reduced in tirofiban group. LVEF value was significantly higher in tirofiban group at 30 days and 180 days compared with those in control group [(51 +/- 6)% vs. (46 +/- 8)%, P < 0.05; (57 +/- 7)% vs. (50 +/- 9)%, P < 0.05]. Hemorrhagic complications were similar between the two groups. CONCLUSION: Use of tirofiban for acute anterior myocardial infarction patients without ST segment resolution after PCI is safe and can significantly improve 30 and 180 days clinical outcomes after discharge.