Sex-based differential regulation of oxidative stress in the vasculature by nitric oxide

Background: Nitric oxide (•NO) is more effective at inhibiting neointimal hyperplasia following arterial injury in male versus female rodents, though the etiology is unclear. Given that superoxide (O2•−) regulates cellular proliferation, and •NO regulates superoxide dismutase-1 (SOD-1) in the vasculature, we hypothesized that •NO differentially regulates SOD-1 based on sex. Materials and methods: Male and female vascular smooth muscle cells (VSMC) were harvested from the aortae of Sprague-Dawley rats. O2•− levels were quantified by electron paramagnetic resonance (EPR) and HPLC. sod-1 gene expression was assayed by qPCR. SOD-1, SOD-2, and catalase protein levels were detected by Western blot. SOD-1 activity was measured via colorimetric assay. The rat carotid artery injury model was performed on Sprague-Dawley rats ±•NO treatment and SOD-1 protein levels were examined by Western blot. Results: In vitro, male VSMC have higher O2•− levels and lower SOD − 1 activity at baseline compared to female VSMC (P < 0.05). •NO decreased O2•− levels and increased SOD − 1 activity in male (P<0.05) but not female VSMC. •NO also increased sod− 1 gene expression and SOD − 1 protein levels in male (P<0.05) but not female VSMC. In vivo, SOD-1 levels were 3.7-fold higher in female versus male carotid arteries at baseline. After injury, SOD-1 levels decreased in both sexes, but •NO increased SOD-1 levels 3-fold above controls in males, but returned to baseline in females. Conclusions: Our results provide evidence that regulation of the redox environment at baseline and following exposure to •NO is sex-dependent in the vasculature. These data suggest that sex-based differential redox regulation may be one mechanism by which •NO is more effective at inhibiting neointimal hyperplasia in male versus female rodents

Fifteen-year experience with renal cell carcinoma with associated venous tumor thrombus.

BACKGROUND: For patients with renal cell carcinoma with venous tumor thrombus (VTT), the importance of the extent of the VTT on survival has inconsistent published results. The aim of the study was to evaluate the prognostic value of the VTT on morbidity and mortality of our patients with renal cell carcinoma. METHODS: This was a single institution review of all patients who underwent resection of renal cell carcinoma with VTT over a 15-year period. RESULTS: Thirty-seven patients (26 men, 11 women) with a mean age of 61 years were analyzed. The majority of the cohort were of Neves level II (n = 19), while 8 were of Neves 0 (only renal vein) or I, and 10 were of Neves III (extending into retrohepatic cava) or IV (extending supradiaphragmatically). When compared with Neves 0-II patients, there were more Neves III-IV patients with operative time \u3e3 hours (70% vs 30%), blood loss \u3e2,000 mL (70% vs 33%), and intensive care unit stay longer than one day (60% vs 30%) (P ≤ .05 each). Mean follow-up was 58 months. The overall 5-year survival was 71%, and all 10 patients with Neves III-IV had survived since the operation. CONCLUSION: We found advanced tumor thrombus involvement did not impact long-term survival; however, cases with suprahepatic VTT had increased operative time, blood loss, and duration of hospital stay