ADAMTS1 and ATP citrate lyase inhibition attenuate connexin-43 degradation and myocyte-myocyte slippage during systolic HFrEF

Previously, in human, we have shown the role of a dis-integrin and metalloproteinase (ADAM) in connexin-43 (Cx43) degradation in human heart end stage heart failure (i.e., heart failure with reduced ejection fraction, HFrEF). We also observed Cx43 degradation and blood heart barrier (BHB) leakage during HFrEF in mice. Although Cx43 coordinates mitochondrial fusion-fission with myocyte contraction-relaxation, respectively, the mechanism is unclear. Interestingly, a mitochondrial ATP citrate lyase inhibition (ACYLi, a lipid lowering agent) mitigated HFpEF, its role in HFrEF is unknown. We hypothesize that during HFrEF activation of ADAMTS1 degrades Cx43, causing dyssynchronous endothelial-myocyte-mitochondrial contraction coupling, and myocytes slippage during contraction and HFrEF. Because HFrEF is more prevalent in males than females, we created chronic cardio-pulmonary volume overload by aorta-vena-cava fistula (AVF) below the kidney in male WT (C57BL/6J) mice of 12-wks old. By serial ..., , # ADAMTS1 and ATP citrate lyase inhibition attenuate connexin-43 degradation and myocyte-myocyte slippage during systolic HFrEF

Dataset DOI: [10.5061/dryad.jsxksn0qh](https://doi.org/10.5061/dryad.jsxksn0qh)

## Description of the data and file structure

**raw-cjpp.pdf**

We analyzed serum matrix metalloproteinases (MMPs) by specific substrate zymography. To determine the expression of ADAMTS, Cx43, TIMP1, ACYL and Drp1, we performed Western blot analysis. The total protein expression levels of ADAMTS1, TIMP1, ACYL, Drp1 and Cx43 were measured by Western blot analysis, using respective antibodies.

The whole gels are presented, and specific respective bands of specific protein are presented.
, ,