Chengxing Shen

Clinical Implication of Coronary Tortuosity in Patients with Coronary Artery Disease

Background Coronary tortuosity (CT) is a common coronary angiography finding. The exact pathogenesis, clinical implication and long-term prognosis of CT are not fully understood. The purpose of this study is to investigate the clinical characteristics of CT in patients with suspected coronary artery disease(CAD) in a Chinese population. Methods A total of 1010 consecutive patients underwent coronary angiography with complaints of chest pain or related symptoms were included in the present study (544 male, mean age: 64±11 years). CT was defined by the finding of ≥3 bends (defined as ≥45° change in vessel direction) along main trunk of at least one artery in systole and in diastole. Patients with or without CAD were further divided into CT-positive and CT-negative groups, all patients were followed up for the incidence of major adverse cardiovascular events (MACE) for 2 to 4 years. Results The prevalence of CT was 39.1% in this patient cohort and incidence of CT was significantly higher in female patients than that in male patients (OR = 2.603, 95%CI 1.897, 3.607, P<0.001). CT was positively correlated with essential hypertension (OR = 1.533, 95%CI 1.131, 2.076, P = 0.006) and negatively correlated with CAD (OR = 0.755, 95%CI 0.574, 0.994, P = 0.045). MACE during follow up was similar between CAD patients with or without CT. Conclusions CT is more often seen in females and positively correlated with hypertension and negatively correlated with coronary atherosclerosis.

Advanced glycation endproducts increase EPC apoptosis and decrease nitric oxide release via MAPK pathways.

OBJECTIVE Previous studies have shown that advanced glycation endproducts (AGE) can induce endothelial progenitor cells (EPC) apoptosis, which contributes to the pathogenesis of diabetes mellitus. Nitric oxide (NO) signaling is closely associated with apoptosis. We therefore investigated the effects of AGE on human EPC apoptosis, NO release and related signal transduction pathways. METHODS EPC isolated from healthy human subjects were cultured with various concentrations of AGE (0, 2, 20 and 200mg/L) for 0, 24, 48 and 72 h in the presence or absence of various MAPK (ERK/P38/JNK) inhibitors, respectively. EPC apoptosis (detected by flow cytometric analyses) and NO concentration in culture supernatant were determined. The mRNA levels of eNOS, COX-2, Bcl-2 and Bax were assessed by RT-PCR and the protein expressions of NF-kappaB and Caspase-3 assessed by Western blot. RESULTS Increased EPC apoptosis and reduced NO release were induced by 200mg/L AGE, accompanied by a downregulation of eNOS and Bcl-2 expressions as well as an elevation in COX-2, Bax, NF-kappaB and Caspase-3 expressions in a time-dependent manner (all P<0.05). These changes were significantly attenuated by pretreatment with various MAPK (ERK/P38/JNK) inhibitors (P<0.05). CONCLUSIONS AGE can promote EPC apoptosis and decrease NO release via MAPK pathways.

Prolonged pain to hospital time is associated with increased plasma advanced oxidation protein products and poor prognosis in patients with percutaneous coronary intervention for ST-elevation myocardial infarction

Plasma advanced oxidation protein products (AOPP) are a biomarker for increased production of reactive oxygen species. We examined the possible association between pain to hospital time, plasma AOPP, and outcome of patients receiving percutaneous coronary intervention (PCI) for ST-elevation acute myocardial infarction (STEMI). Plasma AOPP was determined at hospitalization as well as 24 and 48 h after PCI in 79 patients with suspected STEMI. Patients were stratified into a control group (Group I, n = 21) after exclusion of coronary artery disease, Group II (n = 46) with pain to hospital time <12 h, and Group III (n = 33) with pain to hospital time >12 h. Associations between pain to hospital time and AOPP as well as incidence of major adverse cardiac events (MACE) during 6 months of follow-up were analyzed. Plasma AOPP at admission was significantly higher in patients of Group II (97.58 ± 23.41 μmol/l) and Group III (184.52 ± 30.41 μmol/l) in comparison with Group I (57.41 ± 13.60 μmol/l, all P < 0.001). Plasma AOPP concentration was positively correlated with pain to hospital time and associated with an increased incidence of MACE during the 6-month follow-up period. Prolonged ischemia is associated with increased oxidative stress and poor prognosis in patients treated with PCI for STEMI.

Tissue kallikrein is related to the severity of coronary artery disease

BACKGROUND The impairment of the tissue kallikrein (KLK1)-kinin system (KKS) may result in atheroma development. However, it remains unclear if the KKS correlates with coronary artery disease (CAD). METHODS KLK1, VEGF and hs-CRP plasma levels were measured in 100 patients newly diagnosed with CAD and 33 CAD-free controls. Patients were followed-up for the incidence of major adverse cardiovascular events (MACE) for 8months to 2y. Gene expression of KLK1, CD105 and CD68 was assessed in human coronary endarterectomy specimens. RESULTS Patients with CAD and acute coronary syndrome (ACS) had significantly elevated KLK1 levels. In addition, the concentration of hs-CRP was increased in ACS patients. A strong positive correlation between plasma KLK1 and the severity of CAD was also demonstrated, suggesting that high KLK1 levels are an independent predictor for CAD. MACE during follow-up significantly correlated with KLK1 levels in the ACS group. Unstable coronary plaques demonstrated markedly increased KLK1 levels, macrophage infiltration and high microvessel density. Additionally, KLK1 staining primarily colocalized with macrophages. CONCLUSIONS In the present study, plasma KLK1 levels were a useful predictor for the presence and extent of CAD. More extensive studies are, however, necessary in order to validate these findings.

Tetramethylpyrazine-eluting stents prevented in-stent restenosis in a porcine model.

Objective: Tetramethylpyrazine, a drug originally isolated from the rhizome of Ligusticum walliichi, is an inhibitor of phosphodiesterase and inhibits platelet aggregation and smooth muscle cell proliferation. The effect of the tetramethylpyrazine-eluting stent (TES) on preventing in-stent restenosis was investigated in comparison with control bare metal stents in a porcine coronary stent restenosis model. Methods: The TES was prepared by spray-coating the 2.5 to 3.0 mm × 15 to 20 mm bare metal stents with Tetramethylpyrazine monomer, methyl methacrylate copolymer, and polyglycolic acid. Stent overdilation injury (stent:artery = 1.1 to 1.2:1.0) was made with control bare stents (n = 5) and TES (n = 5) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) and histopathological assessments of stented coronary arteries were performed 4 weeks after stenting. Results: Quantitative coronary angiography showed the late lumen loss (0.28 ± 0.08 mm versus 1.70 ± 0.52 mm; P = 0.004) and percentage diameter stenosis (10.0 ± 2.1% versus 60.2 ± 23.5%; P = 0.01) were significantly lower in the TES group than that in the control group. Histopathological assessments of stented coronary arteries showed that the injury score and the in-stent area were similar between the groups (P > 0.05), whereas the lumen area was significantly larger (4.34 ± 0.93 mm2 versus 1.29 ± 1.02 mm2; P = 0.011) in the TES group than that in the control group. The number of proliferating cell nuclear antigen-positive cells was also significantly decreased in the TES group compared with the control group (14.7 ± 2.5% versus 23.6 ± 3.2%; P = 0.008). Moreover, apoptosis was enhanced in TES group while regrowth of endothelium was similar between the groups. Conclusions: TES inhibited the neointimal hyperplasia and reduced in-stent restenosis in a porcine coronary artery restenosis model.