抄録
Introduction: Prevention of cardiac remodeling induced by myocardial infarction (MI) is of great importance because it is one of the factors for the development of heart failure (HF). Thus, LASSBio-1027 was tested in acute model of MI due to its vasodilatory and anti-proliferative profile through the activation of adenosine A2A and A3 receptors.
Methods: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. MI was induced in male Wistar rats (180-200 g) which were subjected to ligation of the anterior descending coronary artery under isoflorane anesthesia (3% v/v). Animals were randomly divided into groups treated orally (gavage) with either vehicle or LASSBio-1027 (30 and 70 umol/kg) for 7 days. All groups underwent echocardiographic analysis and anterior wall thickness (AWTd) during diastole; mitral flow using the ratio between early transmitral filling velocity (E) and tissue doppler (e,) were determined. The border of infarcted area was used to evaluate interstitial cells and expression of alpha-SMA. Expression of TNF-alpha, SERCA2, p-ERK-1/2 and ERK-1/2 were also investigated. Results: MI reduced AWTd from 1.24 ± 0.17 to 0.42 ± 0.02 mm (P<0.01) which was recovered after treatment with LASSBio-1027. Mitral flow was increased from 22.9 ± 1.6 to 37.0 ± 3.6 (P<0.01) after experimental MI and reduced with LASSBio-1027. The ejection fraction in MI group was 36.6 ± 2.0% which was increased to 46.99 ± 7.40% after treatment (P<0.05). An increase of collagen deposition was observed in MI group of 33.35 ± 5.74% and treatment with LASSBio-1027 (70 µmol/kg) reduced to 14.50 ± 0.32% (P<0.05). LASSBio-1027 reduced interstitial cells from 275.5 ± 49.13 (MI group) to 110.1 ±17.09 (P<0.05). It was observed an increased alpha-SMA expression in the MI group with 36.83 ± 2.89% and a reduction after treatment with LASSBio-1027, 6.28 ± 4.12% and 14.01 ± 4.31%, for 30 and 70 µmol/kg. MI increased the expression of TNF-alpha, p-ERK1-2/ERK1-2 and SERCA2 in comparison to Sham. LASSBio-1027 at 30 μmol/kg recovered the expression of all proteins to control values.
Conclusion: LASSBio-1027 prevented the development of HF by improving cardiac remodeling after acute MI.
