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Anti‐angiogenic role of TIMP‐3 during heart failure
Author(s) -
Givvimani srikanth,
Sen Utpal,
Tyagi Neetu,
Tyagi Suresh
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1096.3
Subject(s) - angiostatin , endostatin , angiogenesis , pressure overload , heart failure , medicine , endocrinology , cardiac function curve , matrix metalloproteinase , muscle hypertrophy , vascular endothelial growth factor , ejection fraction , cardiology , cardiac hypertrophy , vegf receptors
we have reported previously that anti‐angiogenic factors like angiostatin and endostatin play an important role in transition from compensatory cardiac hypertrophy to cardiac failure. Various studies have shown the anti‐angiogenic and pro‐apoptotic role of Tissue inhibitor of matrix metalloproteinase‐3 (TIMP‐3) but its role in generating anti‐angiogenic factors is yet to unveil. We hypothesize that blocking TIMP‐3 expression results in ameliorating the cardiac dysfunction by increase in angiogenesis and decrease in expression of anti‐angiogenic levels. To verify this, aortic banding was done in TIMP‐3 knockout mice to create pressure overload on heart and compared with wild type controls (C57BL6/J) with aortic banding after 8 weeks. Left ventricular function assessed by echocardiography and pressure‐volume studies showed decrease in % fractional shortening and % ejection fraction suggesting the failure stage in wt AB 8 weeks mice compared to TIMP‐3 AB 8 weeks mice. There is increased expression of angiostatin and endostatin along with increased deposition of collagen in wt AB 8 weeks mice compared to TIMP‐3 AB 8 weeks mice. There is increase in expression of vascular endothelial growth factor (VEGF) and CD 31 levels in TIMP‐3 AB 8 weeks mice suggesting the level of angiogenesis. These results show that TIMP‐3 plays an important role in generating anti‐angiogenic factors that lead to heart failure.