| Autor: |
Zapata-Sudo, Gisele, Beltrame, Fabricio, Da Silva, Jaqueline S, Alencar, Allan K, Montagnoli, Tadeu, Maia, Rodolfo, Fraga, Carlos A, Barreiro, Eliezer J, Sudo, Roberto T |
| Zdroj: |
Circulation (Ovid); November 2019, Vol. 140 Issue: Supplement 1 pA15978-A15978, 1p |
| Abstrakt: |
Introduction:The reduction of the inflammatory response characteristic of the acute phase of myocardial infarction (MI) may prevent cardiac remodeling and alter the progression to heart failure.Hypothesis:Activation of adenosine receptors by LASSBio-1027 could interfere with ventricular dysfunction in experimental MI.Methods:MI was induced in male Wistar rats by ligation of the anterior descending coronary artery and confirmed by transthoracic echocardiography. The experimental groups were: Sham, MI and MI + LASSBio-1027. After 7 days of treatment, hemodynamic parameters were evaluated. Fibroblasts were isolated from rat hearts exposed to H2O2and was evaluated the production of collagen in the presence or absence of LASSBio-1027.Results:The filling pressure (E/e?) and the left ventricular end diastolic pressure (LVEDP) were increased in MI group from 22.9 ? 1.6 to 37.0 ? 3.7 and from 3.2 ? 0.9 to 18.2 ? 2.2 mmHg (p<0.01), respectively. LASSBio-1027 (70 ?mol/kg) recovered E/e? and LVEDP to 23.8 ? 5.3 and 6.4 ? 1.6 mmHg (p<0.01). Reduction of 24.1 ? 15.7 and 33.7 ? 9.8% on the hydrogen peroxide-induced collagen production was observed in the presence of 1 and 10 ?M of LASSBio-1027. In cardiac tissue from MI group, it was observed an increase of collagen deposition and interstitial cells which was reduced by LASSBio-1027. Increased expression of alpha-SMA of 36.8 ? 2.9% in the MI group was reduced to 6.3 ? 4.1% after treatment with LASSBio-1027 (70 ?mol/kg). MI increased the expression of TNF-alpha from 21.0 ? 3.0 (Sham) to 40.8 ? 2.1% (p<0.01) and treatment reduced to 25.9 ? 4.0%. The percentage of nuclei staining for c-Fos in Sham was 9.9 ? 2.1 and increased to 24.0 ? 4.7 (p<0.01) in MI group and returned to control value with LASSBio-1027 treatment (9.2 ? 1.3%, p<0.05). Similar results were observed with p-38, iNOS an ERK1-2.Conclusions:LASSBio-1027 improves cardiac function and remodeling induced by MI possibly by attenuating the activation of cardiac fibroblasts. |
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