The Mechanism of Cathepsins S Inhibitor Affected Ischemia-induced Neovascularization in Experimental Mice / 中国循环杂志

Objectives: To investigate the potential mechanism of cathepsins S inhibitor (CatS-I) affected ischemia-induced neovascularization in experimental mice. Methods: 8 week-old wild type (C57/BL6) mice were randomly divided into 2 groups: Control group, the mice received basic diet with intraperitoneal injection of 5% carboxymethylcellulose sodium and CatS-I group, the mice received basic diet with intraperitoneal injection of CatS-I (1mg/kg·d); all animals were treated for 17 days. n=20 in each group. Hind limb ischemia model was established at 3 days after injection in both groups. Blood flow was measured by laser Doppler blood flow analyzer, the ratio of ischemic area to non-ischemic area was calculated; protein expressions of peroxidase proliferation activated receptors-γ (PPAR-γ), p-Akt, p-eNOS and VEGF were examined by Western blot analysis at day 4 after the operation; frozen section of ischemic skeletal muscle was taken at 7 days after operation to measure capillary density by immunohistochemistry.Results: ① CatS-I inhibited blood flow recovery. Compared with Control group, CatS-I group had slower blood flow recovery in ischemic hind limb, P<0.05. ② CatS-I inhibited capillary formation. At 14 days after operation, capillary formation in non-ischemic skeletal muscles was similar between 2 groups, P>0.05; while in ischemic skeletal muscles, capillary density was lower in CatS-I group than Control group, P<0.01. ③ Compared with Control group, CatS-I group showed decreased protein expressions of PPAR-γ, p-Akt, p-Enos and VEGF, P<0.05. Conclusions: CatS-I regulated ischemia-induced neovascularization might be related to PPAR-γ activation and PI3K/Akt/eNOS signaling pathway in experimental mice.

Blood Pressure Variability and Vascular Dysfunction in Essential Hypertension

There are several aspects of blood pressure. Clinically, how to best assess blood pressure average and variability is still a matter of the ongoing debate. Besides office blood pressure, we must pay more careful attention focused on hypertension with blood pressure fluctuation. Impaired endothelial function is intimately associated with the development of hypertension and atherosclerosis. In this review, we describe the relation between endothelial dysfunction and hypertension, the effect of gene polymorphism on endothelial dysfunction, the effects of antihypertensive agents and dietary supplementation on impaired endothelial function in hypertension. In order to predict the future atherosclerosis and cardiovascular events in subjects with hypertension, the adequate assessment of endothelial function is one of the most reliable markers. Furthermore, we discuss the close relationship between blood pressure variability and endothelial function. Blood pressure variability during a day or a week is an important, new risk factor for cardiovascular disease and restoring impaired endothelial function might be a target to prevent blood pressure variation and future cardiovascular events.

Comparison of Bypass Surgery with Drug-Eluting Stents in Diabetic Patients with Left Main Coronary Stenosis

PURPOSE: Several studies have compared the effects of coronary stenting and coronary-artery bypass grafting (CABG) on left main coronary artery (LMCA) disease. However, there are limited data on the long-term outcomes of these two interventions in diabetic patients. MATERIALS AND METHODS: We evaluated 56 patients with LMCA stenosis who underwent drug-eluting stent (DES) implantation and 116 patients who underwent CABG in a single hospital in China between January 2004 and December 2006. We compared long-term major adverse cardiac events (death; a "serious outcome" composite of death, myocardial infarction, or stroke; and target-vessel revascularization). RESULTS: In-hospital (30-day) mortality was 0% for the DES group and 3.4% for the CABG group (p=0.31). There was no difference between the two groups in terms of risk of death [hazard ratio for stenting group, 0.49; 95% confidence interval (CI), 0.13-1.63; p=0.55] or risk of serious outcome (hazard ratio for DES group, 1.11; 95% CI, 0.39-1.45; p=0.47). The target-vessel revascularization rate was higher in the DES group than in the CABG group (hazard ratio, 3.67; 95% CI, 1.24-11.06; p=0.018). CONCLUSION: In this cohort of diabetic patients with LMCA stenosis, there was no difference in composite endpoints between patients receiving DESs and those undergoing CABG. However, stenting was associated with higher rates of target-vessel revascularization than CABG. DES implantation in diabetic patients with LMCA disease was found to be at least as safe as CABG.

Association between lysosomal cysteine protease cathepsin's activation and left ventricular function and remodeling in hypertensive heart failure rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe myocardial cathepsin (Cat) S expression and activity in hypertensive heart failure rats.</p><p><b>METHODS</b>The expression and activity of Cat S were determined in the left ventricular (LV) myocardium (LVM) of Dahl salt-sensitive rats fed either a high-salt (HS, 8%) or low-salt (LS, 0, 3%, controls) diet starting at age 7 weeks for 12 weeks (hypertrophy model, H-LVH) or 19 weeks (heart failure model, H-HF). Age-matched rats served as controls and human normal, hypertensive and heart failure myocardial specimen were also examined for changes on the expression and activity of Cat S.</p><p><b>RESULTS</b>Reverse transcription and real-time polymerase chain reaction analysis revealed significantly upregulated Cat S mRNA in rats with H-HF than in rats with H-LVH or in control rats and Cat S mRNA expression is negatively correlated with LVEF (r = -0.88, P < 0.05). In situ and immunohistochemistry examinations showed that Cat S was localized predominantly in cardiac myocytes (CMCs) and coronary vascular smooth muscle cells (SMC). Elastic lamina fragmentations and Cat S-dependent elastolytic activity were significantly increased in H-HF-rats. The expression of interleukin-1 beta was also increased in the LVM of H-HF rats, and this cytokine was found to increase the Cat S protein expression in culture neonatal CMCs. Similar results were revealed in human myocardial specimens.</p><p><b>CONCLUSION</b>Elastolytic Cat S might play an important role in the pathogenesis of myocardial remodeling and heart failure and Cat S might serve as a novel therapeutic target in preventing or reversing hypertension induced LV remodeling and heart failure.</p>