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Volume 10 Journal of Clinical & Experimental Cardiology
Page 16
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April 29-May 01, 2019 Kyoto, Japan
Heart Congress 2019
April 29-May 01, 2019
4th World Heart Congress
SGLT-2 inhibitors and the heart: Mechanisms of protection
We assessed whether the SGLT-2 inhibitor Dapagliflozin (Dapa) attenuates the upregulation of the cardiac Na+/H+
exchanger (NHE-1) in vitro in mouse cardiofibroblasts stimulated with Lipopolysaccharides (LPS) and whether this
effect is dependent on Adenosine Mono Phosphate Kinase (AMPK) activation. Mouse cardiofibroblasts were exposed for 16
hours to Dapa (0.4 µM), AMPK activator [A769662 (10 μM)], AMPK inhibitor [compound C (CC) (10 μM), an SGLT1 and
SGLT2 inhibitor [phlorizin (PZ) (100 μM)], Dapa+CC or Dapa+PZ and then stimulated with LPS (10 ng/ml) for 3 hours.
NHE-1 mRNA levels were assessed by rt-PCR and total AMPK, phosphorylated-AMPK (P-AMPK), NHE-1 and Heat Shock
Protein-70 (Hsp70) protein levels in the whole cell lysate by immuno blotting. In addition, NHE-1 protein levels attached to
Hsp70 were assessed by immunoprecipitation. Exposure to LPS significantly reduced P-AMPK levels in the cardiofibroblasts.
A769662 and Dapa equally increased P-AMPK. The effect was blocked by CC. Phlorizin had no effect on P-AMPK. LPS
exposure significantly increased NHE-1 mRNA levels. Both Dapa and A769662 equally attenuated this increase. The effect of
Dapa was blocked with CC. Interestingly, none of the compounds significantly affected NHE-1 and Hsp70 protein levels in the
whole cell lysate. However, LPS significantly increased the concentration of NHE-1 attached to Hsp70. Both Dapa and A69662
attenuated this association and CC blocked the effect of Dapa. Again, phlorizin had no effect and did not alter the effect of
Dapa. Dapa increases P-AMPK in cardiofibroblasts exposed to LPS. Dapa attenuated the increase in NHE-1 mRNA and the
association between NHE-1 and Hsp70. This effect was dependent on AMPK.
Biography
Yochai Birnbaum has completed his Master’s from the Hebrew University, Jerusalem, Israel. He is a Professor of Medicine at Baylor College of Medicine, Houston,
Texas. He has published more than 320 papers in reputed journals and has been serving as an Editorial Board Member for many journals.
Yochai Birnbaum
Baylor Collge of Medicine, USA
Yochai Birnbaum, J Clin Exp Cardiolog 2019, Volume 10
DOI: 10.4172/2155-9880-C4-133