Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine.

INTRODUCTION: Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. METHODS: Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D-deficient diet, (2) vitamin D-sufficient diet, and (3) vitamin D-supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. RESULTS: Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D-deficient compared with vitamin D-sufficient or vitamin D-supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D-deficient swine compared with the vitamin D-sufficient or vitamin D-supplemented animal groups. CONCLUSIONS: Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.

Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages.

Inflammatory macrophages play pivotal roles in the development of atherosclerosis. Theranostics, a promising approach for local imaging and photothermal therapy of inflammatory macrophages, has drawn increasing attention in biomedical research. In this study, gold nanorods (Au NRs) were synthesized, and their in vitro photothermal effects on the macrophage cell line (Ana-1 cells) under 808 nm near infrared reflection (NIR) were investigated by the CCK8 assay, calcein AM/PI staining, flow cytometry, transmission electron microscopy (TEM), silver staining and in vitro micro-computed tomography (CT) imaging. These Au NRs were then applied to an apolipoprotein E knockout (Apo E) mouse model to evaluate their effects on in vivo CT imaging and their effectiveness as for the subsequent photothermal therapy of macrophages in femoral artery restenosis under 808 nm laser irradiation. In vitro photothermal ablation treatment using Au NRs exhibited a significant cell-killing efficacy of macrophages, even at relatively low concentrations of Au NRs and low NIR powers. In addition, the in vivo results demonstrated that the Au NRs are effective for in vivo imaging and photothermal therapy of inflammatory macrophages in femoral artery restenosis. This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation-associated diseases.

Excimer laser atherectomy to overcome intraprocedural obstacles in chronic total occlusion percutaneous intervention: Case examples.

Technical advances and the development of the Hybrid algorithm have been associated with higher success rates in chronic total occlusion percutaneous coronary intervention (CTO-PCI). Nevertheless, there are still intraprocedural obstacles that result in failure or prolonged procedure time. The Excimer coronary laser (EL) has been repurposed in CTO-PCI to overcome such obstacles. This case series illustrates the use of the EL in four technically complex scenarios including the balloon resistant lesion, the impenetrable proximal cap, device resistance in stent restenosis, and difficulty with device tracking in the subintima.

A multi-center randomized double-blind placebo-controlled trial of Xiongshao Capsule in preventing restenosis after percutaneous coronary intervention: a subgroup analysis of senile patients.

OBJECTIVE: To evaluate the safety and efficacy of Xiongshao Capsule (XS), consisting of Chuangxiongol and paeoniflorin, in preventing restenosis after percutaneous coronary intervention (PCI) in senile coronary heart disease (CHD) patients. METHODS: A multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 CHD patients were randomly assigned to treatment with oral administration of XS, or a placebo for 6 months after successful PCI. A clinical follow-up was performed at 1, 3 and 6 months after PCI and an angiographic follow-up was scheduled at 6 months. The primary endpoint was angiographic restenosis defined as a luminal stenosis ≥ 50% in follow-up. The secondary endpoints were combined incidence of death, target lesion nonfatal myocardial infarction, repeat target-vessel angioplasty, and coronary artery bypass graft surgery (CABG). The follow-up for the above clinical endpoint events was continued to 1 year after PCI. RESULTS: The subgroup analysis of 152 senile patients (68 cases angiographic follow-up) showed that the restenosis rates tended to reduce in the XS group as compared with that in the placebo group (24.32% vs. 38.71%, P > 0.05), and the minimum lumen diameter (MLD) significantly increased in the follow-up (2.15 ± 0.84 for XS vs. 1.73 ± 0.91 for placebo, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in the XS group (4.11% and 12.33%) as compared with those in the placebo group (17.72% and 43.04%), but there was no significant difference in the combined incidence of clinical outcomes (6.85% in the XS group vs. 11.39% in the placebo group, P > 0.05). No significant adverse reactions occurred within the 6-month follow-up period in the XS group. CONCLUSION: Administration of XS in addition to standardized Western medication for 6 months is demonstrated to be safe and effective in reducing post-PCI recurrent angina and inhibiting luminal restenosis after PCI in senile CHD patients.

Usefulness of intravascular low-power laser illumination in preventing restenosis after percutaneous coronary intervention.

Despite the several years of studies, no factor that could reduce the restenosis rate without significant limitations has been introduced. The aim of the present study was to evaluate the influence of low-power 808-nm laser illumination of coronary vessels after percutaneous angioplasty in preventing restenosis. The procedure of laser intravascular illumination was performed on 52 patients (laser group), and another 49 patients formed the control group. All patients were monitored for major adverse cardiac events (MACE) at the 6- and 12-month follow-up points. The MACE rate after 6 and 12 months was 7.7% in the laser group at both points. The MACE rate was 14.3% and 18.5% at 6 and 12 months of follow-up in the control group, respectively (p = NS). Follow-up coronary angiography was performed after 6 months. The difference in the restenosis rate was insignificant (15.0% vs 32.4%); however, significant differences were observed in the minimal lumen diameter (2.18 ± 0.70 vs 1.76 ± 0.74 mm; p < 0.05), late lumen loss (0.53 ± 0.68 vs 0.76 ± 0.76 mm; p < 0.01), and the late lumen loss index (0.28 ± 0.39 vs 0.46 ± 0.43; p < 0.005) in favor of the laser group. In conclusion, the new therapy seemed effective and safe. Marked differences between late loss, late loss index, and minimal lumen diameter were observed. The late lumen loss in the laser group was only slightly greater than that in studies of drug-eluting stents, and MACE rate remained within very comparable ranges. This suggests that intravascular laser illumination could bring advantages comparable to those of drug-eluting stents without the risk of late thrombosis.

[Study on correlation of blood-stasis syndrome and its accompanied syndromes with pathological changes showed in coronary angiography and restenosis after percutaneous coronary intervention].

OBJECTIVE: To investigate the correlation of blood-stasis syndrome (BSS) and its accompanied syndromes with pathological changes showed in coronary angiography and restenosis after percutaneous coronary intervention (PCI). METHODS: A total of 335 coronary heart disease patients after successful PCI were randomized into the treated group treated with Xiongshao Capsule (XC) and the control group treated with placebo for 6 months. BSS score was evaluated before and 6 months after PCI, and coronary angiography was followed up 6 months after the operation to perform the correlation analysis on BSS and its accompanied syndromes with types and complexity of coronary lesion, and the Logistic multivariate stepwise regression analysis (LMSRA) on the influencing factors of restenosis. RESULTS: There were 334 cases with complete angiographic data, of which 308 cases (91.9%) finished the study, and among them 147 cases received a follow-up with angiography. Correlation analysis showed that the BSS score was significantly correlated to the maximal stenosis degree and coronary lesion score demonstrated by coronary angiography before PCI (P < 0.01), and the correlation was accentuated along with the increasing of the patients' age and the course of disease. Among the accompanied syndromes, the yang-deficiency syndrome was significantly correlated to the complexity of coronary lesions and the degree of stenosis, while the turbid- phlegm syndrome was correlated with calcification of the lesions. The difference of BSS score before and after treatment in the treated group was significantly higher than that in the control group. LMSRA showed that the recurrence of angina and BSS score were the important influencing factors on the occurrence of coronary restenosis after PCI. The incidence of restenosis was not correlated to the accompanied syndromes, and also showed no significant difference among patients with different syndrome types. CONCLUSION: There is a certain correlation between BSS and the complexity of coronary lesions. The lesion is more severe in patients accompanied with yang-deficiency syndrome. The severity of BSS was an important influencing factor on the occurrence of restenosis after PCI, but no significant correlation was found between the occurrence and the type of accompanied syndromes.

Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness, and exercise tolerance: a systematic review.

Greater omega-3 fatty acid consumption is associated with reduced cardiovascular disease risk. Though the mechanisms of their effect are unclear, they may involve lesion formation and heart function. We conducted a systematic review of the clinical literature on the effect of omega-3 fatty acids on measures of vascular structure and function. We included studies that assessed fish and plant sources of omega-3 fatty acids on coronary artery restenosis after angioplasty, carotid IMT, and exercise capacity. Compared to placebo, the summary risk ratio of coronary artery restenosis with fish oil is 0.87 (95% CI 0.73, 1.05) across 12 randomized controlled trials. Two prospective studies reported increased carotid IMT, whereas two cross-sectional studies reported a reduction of IMT, with fish, fish oil or ALA consumption. Three randomized trials and three uncontrolled studies reported small non-significant improvements in exercise capacity with fish oil. Overall, little or no effect of fish oil was found for a variety of markers of cardiovascular disease risk. There are insufficient studies to draw conclusions about the effect of ALA. The dearth of long term data on fish consumption or omega-3 fatty acid supplementation on measures of cardiovascular disease risk severely limits our ability to draw definitive conclusions at this time.

[Increased myocardial blood flow after spinal cord stimulation in patients with refractory angina pectoris]. / Verbesserte myokardiale Durchblutung nach epiduraler Rückenmarkstimulation bei therapierefraktärer Angina pectoris.

BACKGROUND: In spite of great progresses in surgical and catheter interventional techniques there is an increasing number of patients with coronary heart disease not suitable for these conventional treatment strategies. THERAPY: A recent review of the Study Group on the treatment of refractory angina pectoris of the European Society of Cardiology (ESC) recommends spinal cord stimulation (SCS) as first-line therapy. SCS is a well-known and often used therapy for refractory angina in other European countries but not in Germany. The present studies show that SCS is an efficient therapy. By reduction of angina symptoms and a consecutive increase of exercise capacity, the patients experience a great improvement in quality of life. In addition, recent data of our own study suggest a significant decrease in myocardial ischemia in patients under SCS. This might be a direct effect of SCS or due to a better collateralization because of the improved exercise capacity. CONCLUSION: In agreement with the study group of the ESC, we would recommend SCS as first-line therapy for refractory angina pectoris. As a matter of course, conventional treatment strategies should not be replaced by SCS. Hence, a strict evaluation before implanting a SCS device is indispensable.