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Alterations of gene expression in the heart of atrial natriuretic peptide gene‐disrupted (ANP‐/‐) mice following ischemia/reperfusion injury
Author(s) -
Pang Stephen C.,
Tse M. Yat,
Rowe Lindsay,
Liu Xiaoli,
Melo Luis G.
Publication year - 2007
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.21.6.a973-d
Subject(s) - atrial natriuretic peptide , medicine , cardioprotection , reperfusion injury , gene expression , ischemia , myocardial infarction , ligation , endocrinology , gene , biology , biochemistry
Recent evidence suggests a protective role of ANP in myocardial infarction, although the underlying mechanism whereby ANP exerts its cardioprotection is not fully understood. Our preliminary data have shown that ischemia/reperfusion (I/R) injury in ANP‐/‐ mice resulted in an increase in mortality as compared with wide‐type ANP+/+ mice, supporting a cardioprotective role of ANP. In this experiment, we sought to determine the effect of ANP gene disruption on expression of immediate‐early response (cFOS, cJUN), inflammatory (IL‐6), and apoptotic (Bcl‐2, BAX) genes. Ischemia (1 hr)/reperfusion (24 hr) injury was induced by ligation of the anterior interventricular branch of the left coronary artery (LAD) and real‐time PCR was used to quantify gene expression. Our data indicate that in response to I/R injury, ANP‐/‐ mice expressed significantly higher levels of BNP, cJUN and IL‐6 than that of the ANP+/+ mice. Expression of Bcl‐2 and BAX genes remain unchanged in the groups studied. These results suggest that the ANP‐/‐ mice over‐expressed BNP in an attempt to overcome the lack of ANP expression in response to I/R insult. Over‐expression of cJUN and IL‐6 genes may be responsible for the inability of ANP‐/‐ mice to protect the heart against I/R injury. Surprisingly there is no change in the expression of Bcl‐2 and BAX genes 24 hours following I/R injury, although it is possible that over‐expression of these apoptotic genes may come at a later time point. (Supported by Heart and Stroke Foundation of Ontario and the CIHR)