Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abdominal aortic aneurysm is a vascular disease which, despite the fact that it shares common risk factors with atherosclerosis, develops in parallel but as a partly independent process, through different pathogenic mechanisms. The pathogenic mechanisms involve metalloproteinase and collagenase activation, median and adventitial degradation, elastin lysis, vascular smooth cells transformation and apoptosis, collagen production and lysis imbalance combined with excessive inflammatory infiltration. Endothelial cells respond to a number of stimulating factors, including smoking, hypertension and AT1 receptor stimulation and non-uniform distribution of wall stress. Their ability to produce NO is crucial in order to adapt. Endothelial cells contribute to AAA development due to increased oxidative stress which is partly mediated by impaired NO bioavailability due to endothelial dysfunction and NADPH oxidase overexpression. In addition, they express several molecules among which adherence molecules, selectins, endothelin-1, regulating inflammatory infiltration and oxidative stress. Inflammatory cells consist of monocytes, polymorphonuclear neutrophils and lymphocytes and they are involved in the degrading process in the aortic wall by secreting proteolytic enzymes or by releasing interleukins which mediate the inflammation response. Endothelial dysfunction and arterial stiffness reflect on indices like FMD, carotid-femoral PWV and augmentation index, sometimes with controversial results. At present, surgical treatment is the only option provided in patients with large AAA, in particular. Focusing on the emerging role of endothelial cells in AAA pathology may contribute in creating new therapeutic options in a disease which has not yet a well-accepted, implemented pharmaceutical treatment.
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PMID:The Role of Endothelial Dysfunction in Aortic Aneurysms. 2630 38

Endothelial dysfunction is the common molecular basis of multiple human diseases, such as atherosclerosis, diabetes, hypertension, and acute lung injury. Therefore, primary isolation of high-purity endothelial cells (ECs) is crucial to study the mechanisms of endothelial function and disease pathogenesis. Mouse lung ECs (MLECs) are widely used in vascular biology and lung cell biology studies such as pulmonary inflammation, angiogenesis, vessel permeability, leukocyte/EC interaction, nitric oxide production, and mechanotransduction. Thus, in this paper, we describe a simple, and reproducible protocol for the isolation and culture of MLECs from adult mice using collagenase I-based enzymatic digestion, followed by sequential sorting with PECAM1 (also known as CD31)- and ICAM2 (also known as CD102)-coated microbeads. The morphology of isolated MLECs were observed with phase contrast microscope. MLECs were authenticated by CD31 immunoblotting, and immunofluorescent staining of established EC markers VE-cadherin and von Willebrand factor (vWF). Cultured MLECs also showed functional characteristics of ECs, evidenced by DiI-oxLDL uptake assay and THP-1 monocyte adhesion assay. Finally, we used MLECs from endothelium-specific enhancer of zeste homolog 2 (EZH2) knockout mice to show the general applicability of our protocol. To conclude, we describe here a simple and reproducible protocol to isolate highly pure and functional ECs from adult mouse lungs. Isolation of ECs from genetically engineered mice is important for downstream phenotypic, genetic, or proteomic studies.
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PMID:A simple protocol for isolating mouse lung endothelial cells. 3072 72