PADPIN: protein-protein interaction networks of angiogenesis, arteriogenesis, and inflammation in peripheral arterial disease.

Peripheral arterial disease (PAD) results from an obstruction of blood flow in the arteries other than the heart, most commonly the arteries that supply the legs. The complexity of the known signaling pathways involved in PAD, including various growth factor pathways and their cross talks, suggests that analyses of high-throughput experimental data could lead to a new level of understanding of the disease as well as novel and heretofore unanticipated potential targets. Such bioinformatic analyses have not been systematically performed for PAD. We constructed global protein-protein interaction networks of angiogenesis (Angiome), immune response (Immunome), and arteriogenesis (Arteriome) using our previously developed algorithm GeneHits. The term "PADPIN" refers to the angiome, immunome, and arteriome in PAD. Here we analyze four microarray gene expression datasets from ischemic and nonischemic gastrocnemius muscles at day 3 posthindlimb ischemia (HLI) in two genetically different C57BL/6 and BALB/c mouse strains that display differential susceptibility to HLI to identify potential targets and signaling pathways in angiogenesis, immune, and arteriogenesis networks. We hypothesize that identification of the differentially expressed genes in ischemic and nonischemic muscles between the strains that recovers better (C57BL/6) vs. the strain that recovers more poorly (BALB/c) will help for the prediction of target genes in PAD. Our bioinformatics analysis identified several genes that are differentially expressed between the two mouse strains with known functions in PAD including TLR4, THBS1, and PRKAA2 and several genes with unknown functions in PAD including EphA4, TSPAN7, SLC22A4, and EIF2a.

Intra-abdominal hypertension causes reversible blood-brain barrier disruption.

BACKGROUND: Previous studies have shown that intra-abdominal hypertension (IAH) has detrimental effects on organ function and is associated with significantly increased morbidity and mortality. IAH has also been shown to increase intracranial pressure. The exact mechanism is not known. This study tests the effect of an acute increase in intra-abdominal pressure on the permeability of the blood-brain barrier (BBB) in mice. METHODS: Male CD-1 mice weighing 30 g to 38 g were used. Mice in experimental groups underwent either 4 hours of IAH or 4 hours of IAH followed by 1 hour of decompression (DC). A set of control mice were anesthetized for either 4 hours or 5 hours. Femoral artery cannulation was used for blood pressure monitoring. IAH was induced by intraperitoneal infusion of mineral oil to a pressure of 20 mm Hg. DC was performed through an incision in the anterior abdominal wall. BBB integrity was determined by extravasation of 2% Evans blue (EB) dye administered through the femoral vein 1 hour before the mice were killed. BBB permeability was quantified by the EB extravasation method. RESULTS: EB content in brain tissue was higher in the IAH 4-hour group (n = 12) compared with their control group (n = 4; p < 0.05), indicating increased permeability of BBB. In the IAH 4-hour + DC 1-hour group (n = 6), EB content in brain tissue was not significantly higher than their respective control group (n = 6). CONCLUSION: IAH of 20 mm Hg in mice for 4 hours caused increased BBB permeability. This endothelial barrier dysfunction is reversed by abdominal DC.