Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats

Levick, Scott and Loch, David and Rolfe, Barbara E. and Reid, Robert C. and Fairlie, David P. and Taylor, Stephen M. and Brown, Lindsay (2006) Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats. Journal of Immunology, 176 (11). pp. 7000-7007. ISSN 0022-1767


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.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to published version due to publisher copyright policy.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 09 Oct 2011 09:18
Last Modified: 03 Jul 2013 00:43
Uncontrolled Keywords: actins; age factors; cell movement; collagen; echocardiography; endomyocardial fibrosis; enzyme inhibitors; hypertension; hypertrophy; left ventricular; macrophages; monocytes; organ size; pentanoic acids; phospholipases A
Fields of Research : 11 Medical and Health Sciences > 1116 Medical Physiology > 111601 Cell Physiology
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060107 Enzymes
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases

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