| Overexpression of 12-lipoxygenase and cardiac fibroblast hypertrophy. | |
| | |
MedLine Citation:
|
PMID: 12732445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Leukocyte-type 12-lipoxygenase (12-LO) catalyzes the conversion of arachidonic acid (C20:4) to 12-hydroperoxyeicosatetraenoic acid, which in turn reduces to 12-hydroxyeicosatetraenoic acid (12-HETE) by glutathione peroxidase. Results of studies in vascular smooth muscle and in adrenal glomerulosa cells have supported the concept that 12-LO is an important mediator of angiotensin II (Ang II) action. Studies also indicate that 12-HETE is a potent growth-promoting factor and facilitates proliferation in Chinese hamster ovary (CHO) fibroblast cells overexpressing the Ang II AT1a receptor (CHO-AT1a cells). However, until recently, the role of 12-LO in cardiac cells had not been explored. Cardiac fibroblasts are a major source of matrix proteins, which can lead directly to extracellular matrix deposition and cardiac fibrosis. To elucidate the role of the 12-LO pathway in fibroblast cell growth, 12-LO cDNA was stably transfected into fetal rat cardiac fibroblasts. The cells overexpressing 12-LO showed an increase in cell protein content and enlargement in cell size with a slowing of cell division rate. Furthermore, the cells overexpressing 12-LO showed increases in fibronectin and collagen deposition compared with mock-transfected cells. These features are most consistent with cellular hypertrophy instead of proliferation. It is proposed that cardiac fibroblast cells overexpressing 12-LO retain the characteristics of fibroblasts, but with additional features of myocytes that have the function of showing cell hypertrophy. These results provide the basis for proposing the hypothesis that enhanced 12-LO expression or activity could play a role in pathogenic cardiac enlargement. |
| | |
Authors:
|
Yeshao Wen; Jiali Gu; Xianghong Peng; Guoxiang Zhang; Jerry Nadler |
Related Documents
:
|
8960155 - Sensitive response of cultured vascular smooth-muscle cells to cadmium cytotoxicity: co... 16361715 - Epithelioid cell histiocytoma with underlying artery damage. 8508945 - Satellite cells from slow rat muscle express slow myosin under appropriate culture cond... 132225 - Isolation and characterization of myosin from cloned rat glioma and mouse neuroblastoma... 11131515 - The germline in c. elegans: origins, proliferation, and silencing. 16887125 - Measurement of local strain on cell membrane at initiation point of calcium signaling r... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
|
Title: Trends in cardiovascular medicine Volume: 13 ISSN: 1050-1738 ISO Abbreviation: Trends Cardiovasc. Med. Publication Date: 2003 May |
Date Detail:
|
Created Date: 2003-05-06 Completed Date: 2003-09-04 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 9108337 Medline TA: Trends Cardiovasc Med Country: United States |
Other Details:
|
Languages: eng Pagination: 129-36 Citation Subset: IM |
Affiliation:
|
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health Science Center, Charlottesville 22908, USA. yw4w@virginia.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
/
metabolism Animals Arachidonate 12-Lipoxygenase / biosynthesis* Cardiomegaly / metabolism* Fibroblasts / metabolism* Humans Leukocytes / metabolism Leukotrienes / metabolism Muscle, Smooth, Vascular / metabolism, pathology |
| Grant Support | |
ID/Acronym/Agency:
|
R01 DK39721/DK/NIDDK NIH HHS; R01 HL55798/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Leukotrienes; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 67675-13-2/12-HPETE; EC 1.13.11.31/Arachidonate 12-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mind control of menopause.
Next Document: Pathophysiology of human genetic CD36 deficiency.