Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure
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...
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MDPI AG
2021-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/8/1190 |
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| author | Alex Ali Sayour Mihály Ruppert Attila Oláh Kálmán Benke Bálint András Barta Eszter Zsáry Haoran Ke Eszter Mária Horváth Béla Merkely Tamás Radovits |
| author_facet | Alex Ali Sayour Mihály Ruppert Attila Oláh Kálmán Benke Bálint András Barta Eszter Zsáry Haoran Ke Eszter Mária Horváth Béla Merkely Tamás Radovits |
| author_sort | Alex Ali Sayour |
| collection | DOAJ |
| description | 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, <i>n</i> = 12) or volume overload (ACF, <i>n</i> = 12). Sham-operated animals (Sham-T and Sham-A, both <i>n</i> = 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 <i>p</i> < 0.01), whereas the phosphorylation of ERK1/2 was decreased only in ACF; AMPKα activity was significantly reduced in both models. The protein expression of the Nox4 NADPH oxidase isoform was increased in both TAC and ACF compared with respective controls (both <i>p</i> < 0.01), showing a strong positive correlation with SGLT1 expression (<i>r</i> = 0.855, <i>p</i> < 0.001; and <i>r</i> = 0.798, <i>p</i> = 0.001, respectively). Furthermore, SGLT1 protein expression positively correlated with the extent of myocardial nitro-oxidative stress in failing hearts assessed by 3-nitrotyrosin (<i>r</i> = 0.818, <i>p</i> = 0.006) and 4-hydroxy-2-nonenal (<i>r</i> = 0.733, <i>p</i> = 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. |
| first_indexed | 2024-03-10T09:03:20Z |
| format | Article |
| id | doaj.art-6fc80f239e574f9783273b1314965aa7 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:20Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-6fc80f239e574f9783273b1314965aa72023-11-22T06:35:25ZengMDPI AGAntioxidants2076-39212021-07-01108119010.3390/antiox10081190Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart FailureAlex Ali Sayour0Mihály Ruppert1Attila Oláh2Kálmán Benke3Bálint András Barta4Eszter Zsáry5Haoran Ke6Eszter Mária Horváth7Béla Merkely8Tamás Radovits9Heart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryDepartment of Physiology, Semmelweis University, Tűzoltó Str. 37-47, H-1094 Budapest, HungaryDepartment of Physiology, Semmelweis University, Tűzoltó Str. 37-47, H-1094 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryHeart and Vascular Center, Department of Cardiology, Semmelweis University, Városmajor Str. 68, H-1122 Budapest, HungaryMyocardial 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, <i>n</i> = 12) or volume overload (ACF, <i>n</i> = 12). Sham-operated animals (Sham-T and Sham-A, both <i>n</i> = 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 <i>p</i> < 0.01), whereas the phosphorylation of ERK1/2 was decreased only in ACF; AMPKα activity was significantly reduced in both models. The protein expression of the Nox4 NADPH oxidase isoform was increased in both TAC and ACF compared with respective controls (both <i>p</i> < 0.01), showing a strong positive correlation with SGLT1 expression (<i>r</i> = 0.855, <i>p</i> < 0.001; and <i>r</i> = 0.798, <i>p</i> = 0.001, respectively). Furthermore, SGLT1 protein expression positively correlated with the extent of myocardial nitro-oxidative stress in failing hearts assessed by 3-nitrotyrosin (<i>r</i> = 0.818, <i>p</i> = 0.006) and 4-hydroxy-2-nonenal (<i>r</i> = 0.733, <i>p</i> = 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.https://www.mdpi.com/2076-3921/10/8/1190sodium-glucose cotransporter 2 inhibitorsodium-glucose cotransporter 1myocardial nitro-oxidative stressNADPH oxidase 4heart failurepressure overload |
| spellingShingle | Alex Ali Sayour Mihály Ruppert Attila Oláh Kálmán Benke Bálint András Barta Eszter Zsáry Haoran Ke Eszter Mária Horváth Béla Merkely Tamás Radovits Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure Antioxidants sodium-glucose cotransporter 2 inhibitor sodium-glucose cotransporter 1 myocardial nitro-oxidative stress NADPH oxidase 4 heart failure pressure overload |
| title | Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure |
| title_full | Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure |
| title_fullStr | Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure |
| title_full_unstemmed | Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure |
| title_short | Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure |
| title_sort | left ventricular sglt1 protein expression correlates with the extent of myocardial nitro oxidative stress in rats with pressure and volume overload induced heart failure |
| topic | sodium-glucose cotransporter 2 inhibitor sodium-glucose cotransporter 1 myocardial nitro-oxidative stress NADPH oxidase 4 heart failure pressure overload |
| url | https://www.mdpi.com/2076-3921/10/8/1190 |
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