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Comprehensive Assessment of Rosiglitazone on Cardiac Safety in a Rat Model of Heart Failure
Author(s) -
Wang Xinkang,
Liu Xiaorong,
Zhan Yutian,
DiBlasioSmith Liz,
Lavallie Edward R.,
Mounts William,
Winaver Joseph,
Feuerstein Giora Z.
Publication year - 2009
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.23.1_supplement.576.12
Subject(s) - rosiglitazone , medicine , heart failure , endocrinology , ejection fraction , adiponectin , cardiac function curve , valsartan , cardiology , insulin resistance , insulin , blood pressure
The antidiabetic drugs, PPARγ‐modulator class, are associated with severe cardiovascular risk. This liability has not been sufficiently explored in animal models. The present study was designed to assess cardiac safety biomarkers associated with a PPARγ agonist, rosiglitazone (Rosi), in rat heart failure (HF) model. HF was induced by coronary artery ligation and confirmed by ultrasound (US). Sham or HF rats were treated by low (3 mg/kg) or high (45 mg/kg) doses of Rosi, po, for 28 days. Biomarkers for heart structure and function (US), myocardial fibrosis, neuroendocrine biomarkers (BNP, aldosterone) and metabolic variables (glucose and insulin) were monitored. Targeted low‐density gene array was deployed to assess genomic responses. HF was marked by increase in BNP and ANP, low ejection fraction (30‐40%). Rosi effect was confirmed by increase in plasma adiponectin. Genomic analysis of model/treatment effects confirmed suppression by Rosi on ACE and TNFα expression. No evidence on exacerbation of cardiac function, structure and genomic change was noted in HF. ENaCs and Na + /Cl − /K + transporters remained intact while marked increase in PPARγ expression was noted. Our data suggest that Rosi had no adverse effect on cardiac function in rat HF; instead, protective effect was suggested by decrease in ACE and ANP. These data suggest that cardiovascular risk of PPARγ need to be studied in non‐rodent models.