Interleukin-6 (IL-6) is involved in angiogenesis. However, the underlying mechanisms are unknown. Using human cerebral endothelial cell (HCEC), we report for the first time that IL-6 triggers HCEC proliferation and migration in a dose-dependent manner, specifically associated with enhancement of VEGF expression, up-regulated and phosphorylated VEGF receptor-2 (KDR), and stimulated MMP-9 secretion. We investigated the signal pathway of IL-6/IL-6R responsible for KDR's regulation. Pharmacological inhibitor of P13K failed to inhibit IL-6-mediated VEGF overexpression, while blocking ERK1/2 with PD98059 could abolish IL-6-induced KDR overexpression. Further, neutralizing endogenous VEGF attenuated KDR expression and phosphorylation, suggesting that IL-6-induced KDR activation is independent of VEGF stimulation. MMP-9 inhibitor GM6001 significantly decreases HCEC proliferation and migration (p < 0.05), indicating the crucial function of MMP-9 in promoting angiogenic changes in HCECs. We conclude that IL-6 triggers VEGF-induced angiogenic activity through increasing VEGF release, up-regulates KDR expression and phosphorylation through activating ERK1/2 signaling, and stimulates MMP-9 overexpression. (c) 2006 Elsevier Inc. All rights reserved.

The total costs and impacts of expanding energy use in China will depend, in part, on a number of important factors, an understanding of which is vital for China's policy-makers. These issues include the additional environmental and public health impacts associated with energy use, the economic costs of infrastructure expansion to meet growing energy needs, and the potential role that renewable energy technologies could play if pushed hard in China's energy future. This short report summarizes major trends and issues in each of these three areas.

Interleukin- 6 ( IL- 6) may play multiple roles in angiogenesis and vascular remodeling. Our previous study showed that a promoter polymorphism ( 174G > C) in IL- 6 is associated with brain arteriovenous malformation hemorrhage; tissue expression is related to genotype. In this study, we investigated the effects of IL- 6 on human cerebral smooth muscle cells ( HCSMCs) and smooth muscle cells isolated from brain arteriovenous malformation surgical specimens ( AVM SMCs) and surgical controls ( control HCSMCs - from structurally normal temporal lobe taken during surgical treatment of epilepsy patients). We found that IL- 6 ( 1.16 +/- 0.27 versus 0.376 +/- 0.04 pg/ mL, n= 5, P < 0.05) and endogenous vascular endothelial growth factor ( VEGF) receptor II ( kinase domain- containing receptor ( KDR), 15 +/- 3 versus 1.5 +/- 3 pg/ mL, n= 5, P < 0 .05) were increased in brain AVM SMCs compared with control HCSMCs. Further research revealed that IL- 6 could stimulate SMC proliferation, VEGF release, and KDR activation in control HCSMCs. It could also stimulate KDR phosphorylation in control HCSMCs, further confirming a unique role of IL- 6 in the triggering of KDR. Interleukin- 6 could increase matrix metalloproteinase- 9 ( MMP- 9) secretion through activating KDR in control HCSMCs ( P < 0.05 versus control). Inhibiting IL- 6- induced KDR could reduce MMP- 9 activity at least 50% compared with the control group ( P < 0.05). Increased MMP- 9 activity was accompanied by increased control HCSMC proliferation, and blocking MMP- 9 activity significantly reduced IL- 6- induced control HCSMC proliferation ( P < 0.05). Collectively, our results show that IL- 6 could activate, amplify, and maintain the angiogenic cascade in HCSMCs. A novel role of IL- 6 during HCSMC proliferation is upregulating KDR expression and phosphorylation. The results may contribute to the angiogenic phenotype of human brain vascular diseases, such as brain AVM.

China has ambitious goals for economic development, and must find ways to power the achievement of those goals that are both environmentally and socially sustainable. Integration into the global economy presents opportunities for technological improvement and access to energy resources. China also has options for innovative policies and measures that could significantly alter the way energy is acquired and used. These opportunities and options, along with long-term social, demographic, and economic trends, will shape China s future energy system, and consequently its contribution to emissions of greenhouse gases, particularly carbon dioxide (CO2). In this study, entitled China s Sustainable Energy Future: Scenarios of Energy and Carbon Emissions, the Energy Research Institute (ERI), an independent analytic organization under China's Na tional Development and Reform Commission (NDRC), sought to explore in detail how China could achieve the goals of the Tenth Five-Year Plan and its longer term aims through a sustainable development strategy. China's ability to forge a sustainable energy path has global consequences. China's annual emissions of greenhouse gases comprise nearly half of those from developing countries, and 12 percent of global emissions. Most of China's greenhouse gas emissions are in the form of CO2, 87 percent of which came from energy use in 2000. In that year, China's carbon emissions from energy use and cement production were 760 million metric tons (Mt-C), second only to the 1,500 Mt-C emitted by the US (CDIAC, 2003). As China's energy consumption continues to increase, greenhouse gas emissions are expected to inevitably increase into the future. However, the rate at which energy consumption and emissions will increase can vary significantly depending on whether sustainable development is recognized as an important policy goal. If the Chinese Government chooses to adopt measures to enhance energy efficiency and improve the overall structure of energy supply, it is possible that future economic growth may be supported by a relatively lower increase in energy consumption. Over the past 20 years, energy intensity in China has been reduced partly through technological and structural changes; current annual emissions may be as much as 600 Mt-C lower than they would have been without intensity improvements. China must take into account its unique circumstances in considering how to achieve a sustainable development path. This study considers the feasibility of such an achievement, while remaining open to exploring avenues of sustainable development that may be very different from existing models. Three scenarios were prepared to assist the Chinese Government to explore the issues, options and uncertainties that it confronts in shaping a sustainable development path compatible with China's unique circumstances. The Promoting Sustainability scenario offers a systematic and complete interpretation of the social and economic goals proposed in the Tenth Five-Year Plan. The possibility that environmental sustainability would receive low priority is covered in the Ordinary Effort scenario. Aggressive pursuit of sustainable development measures along with rapid economic expansion is featured in the Green Growth scenario. The scenarios differ in the degree to which a common set of energy supply and efficiency policies are implemented. In cons ultation with technology and policy experts domestically and abroad, ERI developed strategic scenarios and quantified them using an energy accounting model. The scenarios consider, in unprecedented detail, changes in energy demand structure and technology, as well as energy supply, from 1998 to 2020. The scenarios in this study are an important step in estimating realistic targets for energy efficiency and energy supply development that are in line with a sustainable development strategy. The scenarios also help analyze and explore ways in which China might slow growth in greenhouse gas emissions. The key results have important policy implications: Depending on how demand for energy services is met, China could quadruple its gross domestic product between 1998 and 2020 with energy use rising by 70 percent to 130 percent (Figure 1). Continual progress in improving the efficiency and structure of industry is crucial to maintaining economic growth with minimal growth in energy use. In some industries, output may grow with no rise in energy use at all. Swelling ranks of motor vehicles will deepen China's dependence on imported oil up to 320 Mt per year by 2020 an amount that global markets can easily supply. To moderate growth in transportation energy use, the strong promotion of convenient public transport will be needed in addition to tighter fuel efficiency standards and advanced vehicles. Fuel switching, efficient appliances, better heating and cooling systems, and improved building envelope technologies will be needed in the fast-growing buildings sector. By 2020, China will still be dependent on coal for 54 percent to 65 percent of its primary energy, even with rapid growth of other fuels and substantial progress in raising the efficiency of coal use. Natural gas supplies, including imported pipeline gas and LNG, will have to expand tremendously to meet demand from households, commercial buildings, and electric utilities; obtaining sufficient supply is a crucial uncertainty. Sustainable growth in electricity generation will require strong policy support for a range of technologies, including advanced coal-fired generation, natural gas, hydropower, non-hydro renewables, and nuclear. If sustainable policies for energy development are not pursued, energy-related carbon emissions could more than double between 1998 and 2020, but if such policies are aggressively pursued carbon emissions could increase by only 50 percent. Although China's energy sector faces many future challenges, it is technically feasible for China to progress towards meeting its development goals while limiting the growth of energy use. However, each of the three scenarios in this report will require significant, long-term policy efforts to achieve the energy and emission trajectories described in the following pages.

Abnormal vascular remodeling mediated by inflammatory cells has been identified as a key pathologic component of various vascular diseases, including abdominal aortic aneurysms, brain arteriovenous malformations and atherosclerosis. Based on findings from observational studies that analysed human intracranial aneurysms and experimental studies that utilized animal models, an emerging concept suggests that a key component of the pathophysiology of intracranial aneurysms is sustained abnormal vascular remodeling coupled with inflammation. This concept may provide a new treatment strategy to utilize agents to inhibit inflammation or cytokines produced by inflammatory cells such as matrix metalloproteinases. Such an approach would aim to stabilize these vascular lesions and prevent future expansion or rupture.