The creation and implementation of a standardized DVT risk assessment program in the electronic medical record significantly increased use of pharmacological and mechanical DVT prophylaxis before surgery in a Veterans Affairs Medical Center setting.

Objective Periadventitial delivery of the nitric oxide (NO) donor PROLI/NO following arterial injury effectively inhibits neointimal hyperplasia. Given the short half-life of NO release from PROLI/NO, our goal was to determine if inhibition of neointimal hyperplasia by PROLI/NO was due to NO, or its metabolites nitrite and nitrate. Methods and Results In vitro, the NO donor DETA/NO inhibited proliferation of rat aortic vascular smooth muscle cells (RASMC), but neither nitrite nor nitrate did. In vivo, following rat carotid artery balloon injury or injury plus the molar equivalents of PROLI/NO, nitrite, or nitrate (n=8–11/group), PROLI/NO was found to provide superior inhibition of neointimal hyperplasia (82% inhibition of intimal area, and 44% inhibition of medial area, p<0.001). Only modest inhibition was noted with nitrite or nitrate (45% and 41% inhibition of intimal area, and 31% and 29% inhibition of medial area, respectively, p<0.001). No effects on blood pressure were noted with any treatment groups. In vivo, only PROLI/NO inhibited cellular proliferation and increased arterial lumen area compared to injury alone (p<0.001). However, all three treatments inhibited inflammation (p<0.001). Conclusions PROLI/NO was more effective at inhibiting neointimal hyperplasia following arterial injury than nitrite or nitrate. However, modest inhibition of neointimal hyperplasia was observed with nitrite and nitrate, likely secondary to anti-inflammatory actions. In conclusion, we have demonstrated that the efficacy of NO donors is primarily due to NO production and not its metabolites, nitrite and nitrate.

The belief that the adventitia serves only a structural purpose has changed over the last decade. Studies have begun to elucidate the role the adventitia plays in the arterial response to injury. The adventitial fibroblast plays an integral part in the development of neointimal hyperplasia. Adiponectin, an adipokine produced from periadventitial adipose tissue, exhibits numerous vasoprotective properties. Stem cells arise, in part, from the adventitia, and stem cell recruitment into the adventitia from the vasa vasorum has been shown to be important in the development of neointimal hyperplasia. The exact role the vasa vasorum plays in neointimal growth is poorly understood and different studies endorse conflicting viewpoints. Thus, understanding the nuances of adventitial pathophysiology will allow us to better appreciate the mechanisms behind the pathology of neointimal hyperplasia. This review will summarize recent findings on the active role the adventitia plays toward the development of neointimal hyperplasia.

Superoxide (O2•−) promotes neointimal hyperplasia following arterial injury. Conversely, nitric oxide (•NO) inhibits neointimal hyperplasia through various cell-specific mechanisms, including redox regulation. What remains unclear is whether •NO exerts cell-specific regulation of the vascular redox environment following arterial injury to inhibit neointimal hyperplasia. Therefore, the aim of the present study was to assess whether •NO exerts cell-specific, differential modulation of O2•− levels throughout the arterial wall, establish the mechanism of such modulation, and determine if it regulates •NO-dependent inhibition of neointimal hyperplasia. In vivo, •NO increased superoxide dismutase-1 (SOD-1) levels following carotid artery balloon injury in a rat model. In vitro, •NO increased SOD-1 levels in vascular smooth muscle cells (VSMC), but had no effect on SOD-1 in endothelial cells or adventitial fibroblasts. This SOD-1 increase was associated with an increase in sod1 gene expression, increase in SOD-1 activity, and decrease in O2•− levels. Lastly, to determine the role of SOD-1 in •NO-mediated inhibition of neointimal hyperplasia, we performed the femoral artery wire injury model in wild type and SOD-1 knockout (KO) mice, with and without •NO. Interestingly, •NO inhibited neointimal hyperplasia only in wild type mice, with no effect in SOD-1 KO mice. In conclusion, these data show the cell-specific modulation of O2•− by •NO through regulation of SOD-1 in the vasculature, highlighting its importance on the inhibition of neointimal hyperplasia. These results also shed light into the mechanism of •NO-dependent redox balance, and suggest a novel VSMC redox target to prevent neointimal hyperplasia.