Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar macrophages play a critical role in the pathophysiology of COPD and are a major target for future anti-inflammatory therapy. Macrophage numbers are markedly increased in the lung and alveolar space of patients with COPD and are localized to sites of alveolar destruction. The increased numbers of macrophages may result from increased recruitment of blood monocytes, prolonged survival in the lung and to a lesser extent to increased proliferation in the lung. Alveolar macrophages from COPD patients have an increased baseline and stimulated secretion of inflammatory proteins, including certain cytokines, chemokines, reactive oxygen species and elastolytic enzymes, which together could account for all of the pathophysiological features of COPD. Alveolar macrophages form COPD appear to be resistant to the anti-inflammatory effects of corticosteriods and this is linked to reduced activity and expression of histone deacetylase 2, a nuclear enzyme that switches off inflammatory genes activated through the transcription factor nuclear factor-KB. Alternative anti-inflammatory therapies that inhibit macrophages are therefore needed in the future to deal with the chronic inflammation of COPD. These drugs may include resveratrol, theophylline derivatives, MAP kinase inhibitors and phosphodiesterase-4 inhibitors.
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PMID:Alveolar macrophages as orchestrators of COPD. 1699 39

Despite the advent of oral phosphodiesterase-5 inhibitors, curative treatment for erectile dysfunction (ED) remains unavailable. Recently, the link between ED and cardiovascular disease was unveiled and the main etiology of ED was found to be vasculogenic. Therefore, neovascularization is a promising strategy for curing ED. Angiopoietin-1 (Ang1) is an angiogenic growth factor that promotes the generation of stable and functional vasculature. Here, we demonstrate that local delivery of the soluble, stable, and potent Ang1 variant, COMP-Ang1 gene or protein, into the penises of hypercholesterolemic mice increases cavernous angiogenesis, eNOS phosphorylation, and cGMP expression, resulting in full recovery of erectile function and cavernous blood flow up to 8 weeks after treatment. COMP-Ang1-induced promotion of cavernous angiogenesis and erectile function was abolished in Nos3(-/-) mice and in the presence of the NOS inhibitor, L-NAME. COMP-Ang1 also restored the integrity of endothelial cell-cell junction by down-regulating the expression of histone deacetylase 2 in the penis of hypercholesterolemic mice and in primary cultured mouse cavernous endothelial cells. These findings constitute a new paradigm toward curative treatment of both cavernous angiopathy and ED.
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PMID:Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouse. 2578 5