Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure
Alex Ali Sayour,
Mihály Ruppert,
Attila Oláh,
Kálmán Benke,
Bálint András Barta,
Eszter Zsáry,
Haoran Ke,
Eszter Mária Horváth,
Béla Merkely,
Tamás Radovits
Affiliations
Alex Ali Sayour
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Mihály Ruppert
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Attila Oláh
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Kálmán Benke
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Bálint András Barta
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Eszter Zsáry
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Haoran Ke
Department of Physiology, Semmelweis University, Tűzoltó Str. 37-47, H-1094 Budapest, Hungary
Eszter Mária Horváth
Department of Physiology, Semmelweis University, Tűzoltó Str. 37-47, H-1094 Budapest, Hungary
Béla Merkely
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Tamás Radovits
Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, Hungary
Myocardial sodium-glucose cotransporter 1 (SGLT1) has been shown to be upregulated in humans with heart failure (HF) with or without diabetes. In vitro studies have linked SGLT1 to increased nitro-oxidative stress in cardiomyocytes. We aimed to assess the relation between left ventricular (LV) SGLT1 expression and the extent of nitro-oxidative stress in two non-diabetic rat models of chronic heart failure (HF) evoked by either pressure (TAC, n = 12) or volume overload (ACF, n = 12). Sham-operated animals (Sham-T and Sham-A, both n = 12) served as controls. Both TAC and ACF induced characteristic LV structural and functional remodeling. Western blotting revealed that LV SGLT1 protein expression was significantly upregulated in both HF models (both p p r = 0.855, p r = 0.798, p = 0.001, respectively). Furthermore, SGLT1 protein expression positively correlated with the extent of myocardial nitro-oxidative stress in failing hearts assessed by 3-nitrotyrosin (r = 0.818, p = 0.006) and 4-hydroxy-2-nonenal (r = 0.733, p = 0.020) immunostaining. Therefore, LV SGLT1 protein expression was upregulated irrespective of the nature of chronic hemodynamic overload, and correlated significantly with the expression of Nox4 and with the level of myocardial nitro-oxidative stress, suggesting a pathophysiological role of SGLT1 in HF.
