Premium
EFFICACY OF THERAPEUTIC ANGIOGENESIS BY INTRAMYOCARDIAL INJECTION OF ADENO‐THIOREDOXIN‐1 IN DIABETIC MYOCARDIUM
Author(s) -
Thirunavukkarasu Mahesh,
Koneru Srikanth,
Penumathsa Suresh Varma,
Zhan Lijun,
Sadoshima Junichi,
Maulik Nilanjana
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.21.5.a528-a
Subject(s) - medicine , angiogenesis , diabetic cardiomyopathy , diabetes mellitus , cardiology , myocardial infarction , therapeutic angiogenesis , streptozotocin , cardioprotection , endocrinology , infarction , neovascularization , cardiomyopathy , heart failure
Diabetes is characterized by decreased collateral vessel formation and treatment that impedes compensatory angiogenesis play a significant role in diabetes induced ischemic cardiomyopathy. We examined the molecular mechanism of impaired angiogenesis in the ischemic myocardium following DM and the therapeutic impact of overexpressing Trx in rat myocardial infarction (MI) model by permanent LAD occlusion. Rats were divided into Control MI (C), Diabetic MI (D), Diabetic + AdLacZ (DLZ) and Diabetic+AdTrx (DT). Diabetes was induced by Streptozotocin (65mg/kg). Four hours after occlusion, AdTrx (1x10 7 ) and AdLacZ was directly injected with an echo‐guided needle into the dysfunctional wall. Reduced infarct size & apoptosis was found in DT compared to D and DLZ. Echocardiographic analysis has shown significant increase in ejection fraction of 62 & 69 in C & DT as compared to 51 and 52 in D & DLZ. Fractional shortening was increased in DT & C (34 & 36) compared to D & DLZ (28 & 30). Decreased left ventricular inner diameter & E/A ratio were observed in DT as compared to D & DLZ. Increased expression of VEGF along with VEGF2 was observed after 4 days in DT. Immunohistochemical analysis demonstrated increased capillary and arteriolar density in DT. Altogether, our results indicate dual effectiveness of Trx in diabetic animals in both promoting angiogenesis and inducing protective as well as regenerative response on cardiac cells.