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

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.