Linked Life Data

17353509

Source:http://linkedlifedata.com/resource/pubmed/id/17353509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-19
pubmed:abstractText
Progressive cardiac remodeling is characterized by subsequent chamber hypertrophy, enlargement, and pump dysfunction. It is also associated with increased cardiac fibrosis and matrix turnover. Interestingly, peroxisome proliferator-activated receptor (PPAR) alpha activators reduce cardiac hypertrophy, inflammation, and fibrosis. Little is known about the role of fenofibrates in mediating PPARalpha-independent effects in response to chronic pressure overload (PO). Wild-type and PPARalpha-deficient mice were subjected to chronic PO caused by ascending aortic constriction to test the role of fenofibrates in chronic, progressive cardiac remodeling by a PPARalpha-independent mechanism. Mice were randomized to regular chow or chow-containing fenofibrate (100 mg/kg of body weight per day) for 1 week before and 8 weeks after ascending aortic constriction. In the presence of PPARalpha, wild-type chronic PO mice, treated with fenofibrate, had improved cardiac remodeling. However, PO PPARalpha-deficient mice treated with fenofibrate had increased mortality, significantly adverse left ventricular end diastolic (3.4+/-0.1 versus 4.2+/-0.1 mm) and end systolic (1.5+/-0.2 versus 2.5+/-0.2 mm) dimensions, and fractional shortening (57+/-3% versus 40+/-3%). Fenofibrate also increased myocardial hypertrophy, cardiac fibrosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2 in PO PPARalpha-deficient mice. Fenofibrate inhibited matrix metalloproteinase activity in vitro and aldosterone-induced increases in extracellular signal-regulated kinase phosphorylation. Thus, fenofibrate improved cardiac remodeling in chronic PO mice. However, in PPARalpha-deficient mice, this chronic PO was exacerbated and associated with increased myocardial fibrosis and altered matrix remodeling. In the absence of PPARalpha, fenofibrates exerts deleterious, pleiotropic myocardial actions. This is an important observation, because PPARalpha agonists are considered possible inhibitory regulators of cardiac remodeling in the remodeled heart.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1084-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17353509-Aldosterone, pubmed-meshheading:17353509-Animals, pubmed-meshheading:17353509-Cells, Cultured, pubmed-meshheading:17353509-Chronic Disease, pubmed-meshheading:17353509-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:17353509-Fenofibrate, pubmed-meshheading:17353509-Fibrosis, pubmed-meshheading:17353509-Hypertension, pubmed-meshheading:17353509-Hypolipidemic Agents, pubmed-meshheading:17353509-Kaplan-Meier Estimate, pubmed-meshheading:17353509-Matrix Metalloproteinase 2, pubmed-meshheading:17353509-Matrix Metalloproteinase 9, pubmed-meshheading:17353509-Mice, pubmed-meshheading:17353509-Mice, Inbred Strains, pubmed-meshheading:17353509-Myocardium, pubmed-meshheading:17353509-Myocytes, Cardiac, pubmed-meshheading:17353509-PPAR alpha, pubmed-meshheading:17353509-Peroxisome Proliferator-Activated Receptors, pubmed-meshheading:17353509-Phosphorylation, pubmed-meshheading:17353509-Time Factors, pubmed-meshheading:17353509-Tissue Inhibitor of Metalloproteinases, pubmed-meshheading:17353509-Ventricular Function, Left
pubmed:year
2007
pubmed:articleTitle
Peroxisome proliferator-activated receptor alpha-independent actions of fenofibrate exacerbates left ventricular dilation and fibrosis in chronic pressure overload.
pubmed:affiliation
Whitaker Cardiovascular Institute, Boston University School of Medicine, MA 02118, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural