Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats. J Immunol 2006 Jun 01;176(11):7000-7
Date
05/20/2006Pubmed ID
16709861DOI
10.4049/jimmunol.176.11.7000Scopus ID
2-s2.0-33646866410 (requires institutional sign-in at Scopus site) 33 CitationsAbstract
The development of fibrosis in the chronically hypertensive heart is associated with infiltration of inflammatory cells and cardiac hypertrophy. In this study, an inhibitor of the proinflammatory enzyme, group IIA human secretory phospholipase A2 (sPLA2-IIA), has been found to prevent collagen deposition as an important component of cardiovascular remodeling in a rat model of developing chronic hypertension. Daily treatment of young male spontaneously hypertensive rats (SHR) with an sPLA2-IIA inhibitor (KH064, 5-(4-benzyloxyphenyl)-4S-(phenyl-heptanoylamino)-pentanoic acid, 5 mg/kg/day p.o.) prevented increases in the content of perivascular (SHR 20.6 +/- 0.9%, n = 5; SHR+KH064 14.0 +/- 1.2%, n = 5) and interstitial (SHR 7.9 +/- 0.3%, n = 6; SHR+KH064 5.4 +/- 0.7%, n = 6) collagen in the left ventricle of rat hearts, but did not affect numbers of infiltrating monocytes/macrophages, left ventricular hypertrophy (SHR 2.88 +/- 0.08, n = 12; SHR+KH064 3.09 +/- 0.08 mg/g body weight, n = 9), increased systolic blood pressure, or thoracic aortic responses. This selective antifibrotic activity suggests that sPLA2-IIA may have an important but specific role in cardiac fibrosis, and that its inhibitors could be useful in dissecting molecular pathways leading to fibrotic conditions.
Author List
Levick S, Loch D, Rolfe B, Reid RC, Fairlie DP, Taylor SM, Brown LMESH terms used to index this publication - Major topics in bold
ActinsAge Factors
Animals
Cell Movement
Collagen
Echocardiography
Endomyocardial Fibrosis
Enzyme Inhibitors
Group II Phospholipases A2
Hypertension
Hypertrophy, Left Ventricular
Macrophages
Male
Monocytes
Organ Size
Pentanoic Acids
Phospholipases A
Phospholipases A2
Rats
Rats, Inbred SHR
Rats, Inbred WKY
