Chymase-dependent angiotensin II formation in the saphenous vein versus the internal thoracic artery

AbstractObjectives: The great saphenous vein graft is known to be less patent than the internal thoracic artery graft. Recently, we reported that chymase-dependent angiotensin II formation plays an important role in the development of intimal hyperplasia in dog grafted veins. In this study we investigated the levels of angiotensin II–forming enzymes, angiotensin-converting enzyme, and chymase in human saphenous veins and internal thoracic arteries. Methods: The saphenous vein and internal thoracic artery specimens were obtained from coronary artery bypass grafts of patients during surgical procedures (saphenous vein, n = 16; internal thoracic artery, n = 16). Activities of angiotensin-converting enzyme and chymase were determined by using the extract from the saphenous vein or internal thoracic artery. Sections of the saphenous vein or internal thoracic artery were stained with van Gieson's elastin stain and were immunostained with anti-human chymase antibody. Results: The activities of angiotensin-converting enzyme in the saphenous vein and internal thoracic artery were 0.34 ± 0.12 and 0.32 ± 0.17 mU/mg protein, respectively, and the difference was not significant. The chymase activity in the saphenous vein was significantly higher than that in the internal thoracic artery (saphenous vein, 10.1 ± 0.81 mU/mg protein; internal thoracic artery, 6.21 ± 1.86 mU/mg protein). Chymase-positive cells in the saphenous vein were located in both the media and adventitia, and those in the internal thoracic artery were located only in the adventitia. The number of chymase-positive cells in the saphenous vein was about 2.6 times that in the internal thoracic artery. Conclusion: The chymase activity, but not the angiotensin-converting enzyme activity, was significantly higher in the saphenous vein, suggesting that the high levels of chymase activity may be related to the poorer performance of the saphenous vein for use as a bypass conduit. (J Thorac Cardiovasc Surg 2001;121:729-34

Prognostic value of ALDH2 polymorphism for patients with oropharyngeal cancer in a Japanese population

<div><p>Background</p><p>Half of Japanese possess a polymorphism of aldehyde dehydrogenase 2(ALDH2), while few white individuals possess this mutation. The purpose of this study was to investigate the possibility of ALDH2 polymorphism as a prognostic factor for oropharyngeal cancer (OPC) among Japanese population.</p><p>Methods</p><p>We analyzed 82 Japanese patients with OPC treated between 2006 and 2011. The median observation period was 50 months. P16-staining and ALDH2 polymorphisms were investigated. To examine the frequencies of second primary pharyngeal and esophageal cancers (SPPEC),37 Japanese patients with OPC treated at Tokyo University Hospital were included for statistical analysis.</p><p>Results</p><p>Statistically significant differences were noted in OS among sex, age, N classification, and p16 (p = 0.045, 0.024, 0.020, 0.007, respectively). In addition, OS and DSS rates of the patients with heterozygous ALDH2 tended to be worse than those of the patients with homozygous ALDH2 (p = 0.21, 0.086, respectively). Of note, OS and DSS of the patients with p16-negative OPC and heterozygous ALDH2 was significant poorer than those of the patients with p16-positive OPC (p = 0.002, 0.006, respectively), while there was no significant difference in OS and DSS between patients with p16-positive OPC and patients with p16-negative OPC and homozygous ALDH2.</p><p>Conclusions</p><p>ALDH2 polymorphism might be a promising prognostic factor for Japanese patients with p16-negative OPC.</p></div

Patients with second primary pharyngeal and esophageal cancers according to p16-status and ALDH2 polymorphism.

<p>Patients with second primary pharyngeal and esophageal cancers according to p16-status and ALDH2 polymorphism.</p

Multivariate analysis of the risk of death.

<p>Multivariate analysis of the risk of death.</p

Survival rates according to three risk-of-death categories.

<p>Survival curves based on Kaplan-Meier estimates of (a) overall survival and (b) disease-specific survival for patients of the low-risk (small dotted line), the intermediate-risk (large dotted line) and the high-risk group (solid line).</p

Overall survival rates according to second primary pharyngeal and esophageal cancers.

<p>Survival curves based on Kaplan-Meier estimates of overall survival for patients with SPPEC (red line) and without SPPEC (black line).</p

Risk-of-Death Categories according to p16-status and ALDH2 polymorphism.

<p>Patients were divided into 3 risk-of-death categories according to p16-status and ALDH2 polymorphism.</p