Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic mice

Venkateswaran Subramanian, Prasanna Krishnamurthy, Krishna Singh, Mahipal Singh

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The purpose of this study was to investigate the role of osteopontin (OPN) in diabetic hearts. Diabetes was induced in wild-type (WT) and OPN knockout (KO) mice by using streptozotocin (150 mg/kg) injection. Left ventricular (LV) structural and functional remodeling was studied 30 and 60 days after induction of diabetes. Induction of diabetes increased OPN expression in cardiac myocytes. Heart weight-to-body weight ratio was increased in both diabetic (D) groups. Lung wet weight-to-dry weight ratio was increased only in the WT-D group. Peak left ventricular (LV) developed pressures measured using Langendorff perfusion analyses were reduced to a greater extent in WT-D versus KO-D group. LV end-diastolic pressure-volume curve exhibited a significant leftward shift in WT-D but not in KO-D group. LV end-diastolic diameter, percent fractional shortening, and the ratio of peak velocity of early and late filling (E/A wave) were significantly reduced in WT-D mice as analyzed by echocardiography. The increase in cardiac myocyte apoptosis and fibrosis was significantly higher in the WT-D group. Expression of atrial natriuretic peptide and transforming growth factor-β1 was significantly increased in the WT-D group. Induction of diabetes increased protein kinase C (PKC) phosphorylation in both groups. However, phosphorylation of PKC-βII was significantly higher in the WT-D group, whereas phosphorylation of PKC-ζ was significantly higher in the KO-D group. Levels of peroxisome proliferator-activated receptor-γ were significantly decreased in the WT-D group but not in the KO-D group. Thus increased expression of OPN may play a deleterious role during streptozotocin-induced diabetic cardiomyopathy with effects on cardiac fibrosis, hypertrophy, and myocyte apoptosis.

Original languageEnglish (US)
Pages (from-to)H673-H683
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Apoptosis
  • Diabetes
  • Fibrosis
  • Heart
  • Hypertrophy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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