ci-1044 and Peripheral-Vascular-Diseases

ci-1044 has been researched along with Peripheral-Vascular-Diseases* in 2 studies

Other Studies

2 other study(ies) available for ci-1044 and Peripheral-Vascular-Diseases

ArticleYear
Investigation of the molecular mechanisms preceding PDE4 inhibitor-induced vasculopathy in rats: tissue inhibitor of metalloproteinase 1, a potential predictive biomarker.
    Toxicological sciences : an official journal of the Society of Toxicology, 2007, Volume: 100, Issue:1

    Phosphodiesterase (PDE) 4 inhibitors are a class of drugs that can provide novel therapies for asthma and chronic obstructive pulmonary disease. Their development is frequently hampered by the induction of vascular toxicity in rat mesenteric tissue during preclinical studies. Whereas these vascular lesions in rats have been well characterized histologically, little is known about their pathogenesis and in turn, sensitive and specific biomarkers for preclinical and clinical monitoring do not exist. In order to investigate the early molecular mechanisms underlying vascular injury, time-course studies were performed by treating rats for 2-24 h with high doses of the PDE4 inhibitor CI-1044. Transcriptomics analyses in mesenteric tissue were performed using oligonucleotide microarray and real-time RT-PCR technologies and compared to histopathological observations. In addition, protein measurements were performed in serum samples to identify soluble biomarkers of vascular injury. Our results indicate that molecular alterations preceded the histological observations of inflammatory and necrotic lesions in mesenteric arteries. Some gene expression changes suggest that the development of the lesions could follow a primary modulation of the vascular tone in response to the pharmacological effect of the compound. Activation of genes coding for pro- and antioxidant enzymes, cytokines, adhesion molecules, and tissue inhibitor of metalloproteinase 1 (TIMP-1) indicates that biomechanical stimuli may contribute to vascular oxidant stress, inflammation, and tissue remodeling. TIMP-1 appeared to be an early and sensitive predictive biomarker of the inflammatory and the tissue remodeling components of PDE4 inhibitor-induced vascular injury.

    Topics: Animals; Azepines; Biomarkers, Pharmacological; Cell Adhesion Molecules; Cluster Analysis; Cytokines; Enzymes; Gene Expression Profiling; Male; Mesenteric Arteries; Niacinamide; Oligonucleotide Array Sequence Analysis; Peripheral Vascular Diseases; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Up-Regulation

2007
Bringing biomarkers to the masses: an elegant approach to discover potential biomarkers of vascular injury.
    Toxicological sciences : an official journal of the Society of Toxicology, 2007, Volume: 100, Issue:1

    Topics: Animals; Azepines; Biomarkers, Pharmacological; Cell Adhesion Molecules; Cluster Analysis; Cytokines; Enzymes; Gene Expression Profiling; Humans; Mesenteric Arteries; Niacinamide; Oligonucleotide Array Sequence Analysis; Peripheral Vascular Diseases; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Rats; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; RNA, Messenger; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Up-Regulation

2007