Effects of rosuvastatin on expression of angiotensin-converting enzyme 2 after vascular balloon injury in rats

Objective To investigate the effects and mechanisms of rosuvastatin on angiotensin -converting enzyme 2 (ACE2) in the process of neointimal formation after vascular balloon injury in rats, and to explore the effects of ACE2 and rosuvastatin in restenosis. Methods Thirty-six Wistar rats were randomly allocated into three groups: control group (n = 12), surgery group (n = 12), and statin group (n = 12). Aortic endothelial denudation of rats was performed using 2F balloon catheters. At days 14 and 28 after injury, aortic arteries were harvested to examine the following. Intimal thickening was examined by hematoxylin and eosin staining. We measured angiotensin II (Ang II) and angiotensin 1-7 (Ang-[1–7]) levels by a radioimmunological method or enzyme-linked immunosorbent assay. Protein andmRNAexpression of ACE2 and Ang II type 1 receptor (AT1) were investigated by immunohistochemistry, Western blots, and Reverse transcriptase- polymerase chain reaction (RT-PCR). We measured changes in proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The level of phosphorylated extracellular signal regulated kinase 1/2 (P-ERK1/2) was evaluated byWestern blotting. Results Proliferation of vascular smooth muscle cells (VSMC) and intimal thickening were higher at day 14 after vascular balloon injury in the surgery group compared with the control group. Proliferation of VSMC was decreased by day 28 after injury, while intimal thickening continued. With rosuvastatin treatment, the extent of VSMC proliferation and intimal thickening was reduced at day 14 and 28 after injury. Ang II and P-ERK levels were significantly increased, Ang-(1–7) levels were significantly decreased, mRNA and protein expressions of ACE2 were significantly decreased, and AT1 expression was significantly increased at days 14 and 28 after vascular balloon injury in the surgery group compared with the control group. PCNAexpression was higher in the surgery group than in the control group, and it was significantly decreased after being given rosuvastatin. Expression of ACE2 mRNA and protein, and Ang-(1–7) levels were significantly increased, while AT1 expression and levels of Ang II and P-ERK were significantly decreased in the statin group compared with the surgery group. Conclusions Expression of ACE2 mRNA and protein is decreased in the process of intimal thickening after balloon injury. The inhibitory effect of rosuvastatin on intimal thickening is related to upregulation of ACE2, an increase in Ang-(1–7), downregulation of AT1, and activation of the P-ERK pathway.

Implantable defibrillator lead extraction with optimized standard extraction techniques

Background Implantable cardioverter-defibrillator (ICD) leads might not be extracted especially in developing countries because of the high cost and lack of specialized tools. We aimed to evaluate transvenous extraction of ICD leads using optimized standard techniques. Methods We prospectively analyzed clinical characteristics, optimized extraction techniques and the feasibility of extraction for 40 patients (33 males; mean age 47.9 ±16.1 years) with 42 ICD leads. Results Complete procedural success rate was 95.2% (40/42), and the clinical success rate was 97.6% (41/42). One ICD lead required cardiothoracic surgery. Minor complications occurred in three cases (7.5%), and no major complications or death occurred. Locking stylets were used to extract most leads (34, 81.0%) and almost half of the leads (20, 47.6%) required mechanical dilatation to free fibrotic adhesions; these leads had been implanted for a longer period of time than the others (43.7 ± 18.2 vs. 18.4 ±13.4 months, P < 0.05). Three-quarters of the leads (30, 71.4%) were extracted with locking stylets plusmanual traction (12, 28.6%), or mechanical dilatation with counter-traction (18, 42.8%) by the superior vena cava approach and one-quarter of the leads (11, 26.2%) were removed by optimized snare techniques using the femoral vein approach. Median extraction time was 20 min (range 2–68 min) per lead. Linear regression analysis showed that the extraction time was significantly correlated with implant duration (r = 0.70, P < 0.001). Median follow-up was 14.5months (range 1–58 months), no infection, or procedure-related death occurred in our series. Conclusions Our optimized procedure for transvenous extraction of ICD leads provides a practical and low-costmethod for standard procedures.