α1A-Adrenoreceptor blockade attenuates myocardial infarction by modulating the integrin-linked kinase/TGF-β/Smad signaling pathways

Abstract

Abstract Background The role of α1A-adrenoceptor inhibition or its relationship with integrin-linked kinase (ILK) and transforming growth factor-beta (TGF-β)/small mothers against decapentaplegic (Smad) signaling pathways in attenuating myocardial infarction (MI) is unclear. Objectives To investigate whether tamsulosin, an α1A-adrenoceptor blocker, attenuates MI via modulation of an ILK-related TGFβ/Smad pathway. Methods Twenty-four adult male Wistar rats (150−250 g) were randomly divided into four groups: 1) control group, which received a 0.9% NaCl solution orally for 21 days; 2) tamsulosin-treated group, which received tamsulosin (0.8 mg/kg) for 21 days; 3) isoproterenol (ISO)-treated group, which received 0.9% NaCl for 21 days and ISO (150 mg/kg, ip) injected on days 20 and 21 to induce MI; and 4) tamsulosin + ISO group, treated with tamsulosin for 21 days followed by two ISO injections on two consecutive days. The heart/body weight ratios and cardiac and fibrotic biomarker levels were subsequently measured. ILK, TGF-β1, p-Smad2/3, and collagen III protein expression levels were determined using biomolecular methods. Results Tamsulosin significantly attenuated the relative heart-body index (p < 0.5) and creatine kinase (CK)-MB levels (p < 0.01) compared to the ISO control group. While ISO produced superoxide anions and enhanced oxidative damage, tamsulosin treatment significantly prevented this damage via antioxidant defenses, increasing glutathione and superoxide dismutase levels (p < 0.05) and decreasing lipid peroxide oxidation levels (p < 0.01). Data revealed that tamsulosin reduced expression of TGF-β/p-Smad2/3 and enhanced ILK expression. Conclusion Tamsulosin may exert a cardioprotective effect by modulating the ILK-related TGF-β/Smad signaling pathway. Thus, tamsulosin may be a useful therapeutic approach for preventing MI.