Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats
Article
Article Title | Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats |
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ERA Journal ID | 15513 |
Article Category | Article |
Authors | Levick, Scott (Author), Loch, David (Author), Rolfe, Barbara E. (Author), Reid, Robert C. (Author), Fairlie, David P. (Author), Taylor, Stephen M. (Author) and Brown, Lindsay (Author) |
Journal Title | Journal of Immunology |
Journal Citation | 176 (11), pp. 7000-7007 |
Number of Pages | 8 |
Year | 2006 |
Place of Publication | Bethesda, MD. United States |
ISSN | 0022-1767 |
1550-6606 | |
Web Address (URL) | http://www.jimmunol.org/content/176/11/7000.full.html#related-urls |
Abstract | 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. |
Keywords | actins; age factors; cell movement; collagen; echocardiography; endomyocardial fibrosis; enzyme inhibitors; hypertension; hypertrophy; left ventricular; macrophages; monocytes; organ size; pentanoic acids; phospholipases A |
ANZSRC Field of Research 2020 | 320801. Cell physiology |
310106. Enzymes | |
320101. Cardiology (incl. cardiovascular diseases) | |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | University of Queensland |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q0w66/antifibrotic-activity-of-an-inhibitor-of-group-iia-secretory-phospholipase-a2-in-young-spontaneously-hypertensive-rats
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