Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

Watershed urbanization alters the composition and function of stream bacterial communities.

Watershed urbanization leads to dramatic changes in draining streams, with urban streams receiving a high frequency of scouring flows, together with the nutrient, contaminant, and thermal pollution associated with urbanization. These changes are known to cause significant losses of sensitive insect and fish species from urban streams, yet little is known about how these changes affect the composition and function of stream microbial communities. Over the course of two years, we repeatedly sampled sediments from eight central North Carolina streams affected to varying degrees by watershed urbanization. For each stream and sampling date, we characterized both overall and denitrifying bacterial communities and measured denitrification potentials. Denitrification is an ecologically important process, mediated by denitrifying bacteria that use nitrate and organic carbon as substrates. Differences in overall and denitrifying bacterial community composition were strongly associated with the gradient in urbanization. Denitrification potentials, which varied widely, were not significantly associated with substrate supply. By incorporating information on the community composition of denitrifying bacteria together with substrate supply in a linear mixed-effects model, we explained 45% of the variation in denitrification potential (p-value<0.001). Our results suggest that (1) the composition of stream bacterial communities change in response to watershed urbanization and (2) such changes may have important consequences for critical ecosystem functions such as denitrification

Fetal congenital heart disease and intrauterine growth restriction: a retrospective cohort study

Fetal congenital heart disease may lead to abnormal fetal growth. Our objective was to estimate the association between fetal congenital heart disease (CHD) and intrauterine growth restriction (IUGR) in an effort to better inform clinical management of continuing pregnancies complicated by fetal congenital heart disease. In a retrospective cohort study, outcome data was collected from singleton pregnancies undergoing routine anatomic survey at a tertiary medical center between 1990 and 2008. Dedicated research nurses collected information on delivery outcomes in an on-going manner. Subjects with a prenatal diagnosis of fetal CHD were compared to those without CHD. Stratified analyses for isolated fetal CHD and major CHD were performed. The primary outcome was IUGR less than 10th percentile by the Alexander growth standard. Logistic regression was used to adjust for confounding variables and refine the estimates of risk. Among 67,823 patients, there were 193 cases of fetal CHD (0.3%) and 5,669 cases of IUGR (8.4%). Prenatal diagnosis of CHD was associated with an increased risk of IUGR (23.8% vs. 8.5%, adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 2.4-4.6), and the risk was greatest in fetuses with major CHD (16.5% vs. 8.5%, aOR 2.1, 95% CI 1.3-3.2). Isolated CHD was also associated with an increased risk of IUGR (17.8% vs. 8.5%, aOR 2.2, 95% CI 1.4-3.7). Patients with a prenatal diagnosis of fetal CHD have a three-fold increase in risk of developing IUGR; patients with isolated fetal CHD are twice as likely to develop IUGR. Based on our findings, serial growth assessment may be a reasonable option for patients with fetal CHD diagnosed at routine anatomic survey