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

ABSTRACT: 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.

SUBMITTER: Chu LH

PROVIDER: S-EPMC4525078 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Chu Liang-Hui LH Vijay Chaitanya G CG Annex Brian H BH Bader Joel S JS Popel Aleksander S AS

Physiological genomics 20150609 8

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 analyse ...[more]

PMID: 26058837

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Project description:BACKGROUND AND PURPOSE:Encephaloduroarteriosynangiosis has been shown to generate collateral vessels from the extracranial-to-intracranial circulation in patients with Moyamoya disease and intracranial arterial steno-occlusive disease. The mechanisms involved are not well-understood. We hypothesized that angiogenesis is the leading mechanism forming collaterals after encephaloduroarteriosynangiosis because there are no pre-existing connections. Angiogenesis-generated collaterals should exhibit higher architectural complexity compared with innate collaterals. MATERIALS AND METHODS:Pre- and postoperative digital subtraction angiograms were analyzed in patients enrolled in a prospective trial of encephaloduroarteriosynangiosis surgery. Branching angioscore, tortuosity index, and local connected fractal dimension were compared between innate and postoperative collaterals. RESULTS:One hundred one angiograms (50 preoperative, 51 postoperative) were analyzed from 44 patients (22 with intracranial atherosclerosis and 22 with Moyamoya disease). There was a significantly higher median branching angioscore (13 versus 4, P < .001) and a lower median tortuosity index (1.08 versus 1.76, P < .001) in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals. Higher mean local fractal dimension peaks (1.28 ± 0.1 versus 1.16 ± 0.11, P < .001) were observed in the encephaloduroarteriosynangiosis collaterals compared with innate collaterals for both intracranial atherosclerosis (P < .001) and Moyamoya disease (P < .001) groups. The observed increase in high connectivity was greater in the intracranial atherosclerosis group compared with patients with Moyamoya disease (P = .01). CONCLUSIONS:The higher median branching angioscore and local connected fractal dimension, along with the lower median tortuosity index of encephaloduroarteriosynangiosis collaterals, are consistent with the greater complexity observed in the process of sprouting and splitting associated with angiogenesis.

Dataset Information

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

Publications

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

Similar Datasets

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