AI Article Synopsis

  • - Myocardial sodium-glucose cotransporter 1 (SGLT1) is increased in heart failure (HF) patients, whether they have diabetes or not, and is linked to heightened nitro-oxidative stress in heart cells.
  • - In a study using non-diabetic rat models of chronic HF induced by pressure or volume overload, SGLT1 expression was notably higher, and related to increased levels of Nox4 and myocardial nitro-oxidative stress.
  • - The findings suggest that SGLT1 plays a significant role in the pathology of heart failure, as its expression correlates with increased oxidative stress markers in failing hearts.

Article Abstract

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, = 12) or volume overload (ACF, = 12). Sham-operated animals (Sham-T and Sham-A, both = 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 < 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 < 0.01), showing a strong positive correlation with SGLT1 expression ( = 0.855, < 0.001; and = 0.798, = 0.001, respectively). Furthermore, SGLT1 protein expression positively correlated with the extent of myocardial nitro-oxidative stress in failing hearts assessed by 3-nitrotyrosin ( = 0.818, = 0.006) and 4-hydroxy-2-nonenal ( = 0.733, = 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388925PMC
http://dx.doi.org/10.3390/antiox10081190DOI Listing

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