Chronic irradiation with low-dose-rate 137Cs-γ rays inhibits NGF-induced neurite extension of PC12 cells via Ca2+/calmodulin-dependent kinase II activation.

Chronic irradiation with low-dose-rate 137Cs-γ rays inhibits the differentiation of human neural progenitor cells and influences the expression of proteins associated with several cellular functions. We aimed to determine whether such chronic irradiation influences the expression of proteins associated with PC12 cells. Chronic irradiation at 0.027 mGy/min resulted in inhibition of NGF-induced neurite extension. Furthermore, irradiation enhanced the nerve growth factor (NGF)-induced increase in the phosphorylation of extracellular signal-regulated kinase (ERK), but did not affect the phosphorylation of NGF receptors, suggesting that irradiation influences pathways unassociated with the activation of ERK. We then examined whether irradiation influenced the Akt-Rac1 pathway, which is unaffected by ERK activation. Chronic irradiation also enhanced the NGF-induced increase in Akt phosphorylation, but markedly inhibited the NGF-induced increase in Rac1 activity that is associated with neurite extension. These results suggest that the inhibitory effect of irradiation on neurite extension influences pathways unassociated with Akt activation. As Ca2+/calmodulin-dependent kinase II (CaMKII) is known to inhibit the NGF-induced neurite extension in PC12 cells, independent of ERK and Akt activation, we next examined the effects of irradiation on CaMKII activation. Chronic irradiation induced CaMKII activation, while application of KN-62 (a specific inhibitor of CaMKII), attenuated increases in CaMKII activation and recovered neurite extension and NGF-induced increases in Rac1 activity that was inhibited by irradiation. Our results suggest that chronic irradiation with low-dose-rate γ-rays inhibits Rac1 activity via CaMKII activation, thereby inhibiting NGF-induced neurite extension.

The Role of Optical Coherence Tomography in Coronary Intervention

Optical coherence tomography (OCT) is an optical analog of intravascular ultrasound (IVUS) that can be used to examine the coronary arteries and has 10-fold higher resolution than IVUS. Based on polarization properties, OCT can differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identify thin-cap fibroatheroma. Because of the strong attenuation of light by blood, OCT systems required the removal of blood during OCT examinations. A recently developed frequency-domain OCT system has a faster frame rate and pullback speed, making the OCT procedure more user-friendly and not requiring proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT can provide detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition [ISA]). At follow-up examinations after stent implantation, stent strut coverage and ISA can be assessed. Several OCT studies have demonstrated delayed neointimal coverage following drug-eluting stent (DES) implantation vs. bare metal stent (BMS) placement. While newer DESs promote more favorable vascular healing, the clinical implications remain unknown. Recent OCT studies have provided insights into restenotic tissue characteristics; DES restenotic morphologies differ from those with BMSs. OCT is a novel, promising imaging modality; with more in-depth assessments of its use, it may impact clinical outcomes in patients with symptomatic coronary artery disease.

Neointimal coverage of sirolimus-eluting stents 6 months and 12 months after implantation: evaluation by optical coherence tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Optical coherence tomography (OCT) is a new imaging modality with resolution of approximately 10 microm and can be employed to visualize intracoronary characteristics. Sirolimus-eluting stents (SES) are susceptible to late thrombosis due to delayed re-endothelialization over the stent struts, which may result in acute myocardial infarction or death. This study was designed to evaluate the re-endothelialization and neointimal coverage of SES with OCT 6 months and 12 months after implantation.</p><p><b>METHODS</b>A total of 36 patients enrolled in the study underwent OCT examination 6 months (17 patients) and 12 months (19 patients) after SES implantation. The strut apposition to the vessel wall and neointimal coverage on SES struts were evaluated by OCT.</p><p><b>RESULTS</b>Forty-six SES and 6561 struts were analyzed. At 6 months, 3041 struts (98.7%) were well-apposed and 39 struts (1.3%) were malapposed. At 12 months, 3434 struts (98.6%) were well-apposed and 47 struts (1.4%) were malapposed. Furthermore, only 4 SES at 6 months (18.2%) and 10 SES at 12 months (41.7%) were fully covered by neointimal growth. The average neointimal thicknesses covering the analyzed struts at 6 months and 12 months were (42+/-28) microm and (88+/-32) microm, respectively. There were 1989 struts at 6 months (72.1%) and 1461 struts at 12 months (45.6%) with neointimal thickness <100 microm.</p><p><b>CONCLUSIONS</b>OCT was able to visualize the strut apposition to the vessel wall and neointimal coverage on SES struts. At 6-month and 12-month follow-up examinations most struts were covered with thin neointima, but few of the entire SES showed full coverage. To prevent late-stent thrombosis in the presence of uncovered stent struts, longer dual antiplatelet drugs therapy should be recommended.</p>