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Role of dicer in diabetic cardiomyopathy through dysregulation of MMP‐9 and TIMP‐4
Author(s) -
Mishra Paras Kumar,
Givvimani Srikanth,
Sen Utpal,
Abe Oluwasegun A,
Tyagi Neetu,
Basu Poulami,
Munjal Charu,
Tyagi Suresh C
Publication year - 2010
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.24.1_supplement.978.19
Subject(s) - dicer , medicine , matrix metalloproteinase , endocrinology , dilated cardiomyopathy , cardiomyopathy , diabetic cardiomyopathy , western blot , heart failure , chemistry , small interfering rna , biochemistry , rna , gene
To test the hypothesis that dysregulation of matrix metalloproteinase‐9 (MMP‐9) and its tissue inhibitor (TIMP‐4) causes diabetic cardiomyopathy is regulated by dicer, 10 weeks old male Ins2‐/+ Akita and C57 BL/6J mice were used to assess gravimetric parameters, physiological status of heart using pressure‐volume (P‐V) loop and echocardiography. Expression of GLUT‐4, MMP‐9, TIMP‐4 and dicer‐ a microRNA maturation enzyme was measured by RT‐PCR and Western Blot. Further, Akita mice were treated with folic acid (0.03 g/l) for 4 wks. The results revealed that Akita mice were hyperglycemic (>300 mg/dl) with low body weight/heart weight ratio as compared to control. Dilated cardiomyopathy of Akita mice was evident through echocardiography where systolic diameter was increased and fractional shortening was decreased. Additionally, impairment of ventricular contractility in Akita mice was confirmed by shift of P‐V loop towards right hand side. There was robust increase in MMP‐9 and dicer expression in Akita mice while TIMP‐4 and GLUT‐4 were decreased. Interestingly, folic acid treated Akita mice showed amelioration of MMP‐9 and TIMP‐4 expression. Based on these findings, we conclude that balance between MMP‐9 and TIMP‐4 is crucial for diabetic cardiomyopathy where dicer plays a regulatory role, and folic acid have therapeutic implications.