Dataset DOI: 10.5061/dryad.prr4xgz2g

Description of the data and file structure

Files and variables

File: Fig1_data_Morphometry.xlsx

Description: This file contains morphometric data of leptin receptor (Lepr)-deficient db/db mice with chronic aldosterone infusion (db/db+Aldo) that induced heart failure with preserve ejection fraction (HFpEF) and in vehicle-treated wild-type mice (WT+Veh) chronically treated with empagliflozin (Empa) in vivo for 4 weeks. Data structure follows presentation on Figure 1 in the referenced article, and data in each figure panel is included in separate excel sheets. "Panel B" section provides data for blood glucose levels (in millimoles per liter), body mass (in grams), plasma B-type natriuretic peptide (BNP, in picograms per liter), and pulmonary oedema (quantified as wet to dry lung weight ratio). "Panel C" section provides data for cardiac hypertrophy (quantified as heart weight to tibial length ratio, HW/TL, in grams per millimeter), hepatomegaly (liver weight in grams), kidney weight (in grams), and sarcopenia (quantified as combined gastrocnemius and soleus muscle weights in grams). One male db/db+Aldo mouse (not treated with empagliflozin) died before the conclusion of the study protocol and the missing data is labelled with "n/a".

Variables

• Blood glucose levels (in millimoles per liter)
• Body mass (in grams)
• B-type natriuretic peptide (BNP, in picograms per liter)
• Pulmonary oedema (quantified as wet to dry lung weight ratio)
• Cardiac hypertrophy (quantified as heart weight to tibial length ratio, HW/TL, in grams per millimeter)
• Hepatomegaly (liver weight in grams)
• Kidney weight (in grams)
• Sarcopenia (quantified as combined gastrocnemius and soleus muscle weights in grams)

File: Fig2_data_Echocardiography.xlsx

Description: This file contains data with transthoracic echocardiography data in leptin receptor (Lepr)-deficient db/db mice with chronic aldosterone infusion (db/db+Aldo) that induced heart failure with preserve ejection fraction (HFpEF) and in vehicle-treated wild-type mice (WT+Veh) chronically treated with empagliflozin (Empa) in vivo for 4 weeks. Data structure follows presentation on Figure 2 in the referenced article, and data in each figure panel is included in separate excel sheets. “Panel B” section provides data on systolic heart function parameters: ejection fraction (EF, %), fractional shortening (FS, %), left ventricular internal diameter at diastole (LVIDd, in millimeters), and left ventricular posterior wall thickness at diastole (LVPWd, in millimeters). “Panel C” section provides data on cardiac hypertrophy and diastolic heart function parameters: left ventricular (LV) mass (in milligrams), early to late filling velocity ratio (ratio between mitral E wave and A wave, E/A), ratio between mitral E wave and e’ wave (E/e'), and left atrial (LA) area (in square millimeters). One male db/db+Aldo mouse (not treated with empagliflozin) died before the conclusion of the study protocol and the missing data is labelled with "n/a".

Variables

• Ejection fraction (EF, in percentage)
• Fractional shortening (FS, in percentage)
• Left atrial area (LA area, in square millimeters)
• Left ventricular internal diameter at diastole (LVIDs, in millimeters)
• Left ventricular mass (LV Mass, in milligrams)
• Early to late filling velocity ratio (ratio between mitral E wave and A wave, E/A)
• Ratio between mitral E wave and e’ wave (E/e')
• Left ventricular posterior wall thickness at diastole (LVPWd, in millimeters)

File: Fig3_data_AP-parameters.xlsx

Description: This file contains data on ventricular cardiomyocyte action potentials (APs) in leptin receptor (Lepr)-deficient db/db mice with chronic aldosterone infusion (db/db+Aldo) that induced heart failure with preserve ejection fraction (HFpEF) and in vehicle-treated wild-type mice (WT+Veh) chronically treated with empagliflozin (Empa) in vivo for 4-wks. Data structure follows presentation on Figure 3 in the referenced article, and data in each figure panel is included in separate excel sheets. “Panel A” section provides typical AP waveforms data (time in milliseconds and membrane voltage in millivolts) at 1 Hz steady-state pacing. “Panel B” section provides fifty consecutive AP duration at 90% repolarization (APD₉₀) data at 1 Hz steady-state pacing (time in seconds, APD₉₀ in milliseconds) and the frequency-dependence of APD₉₀ (pacing rate in Hertz, APD₉₀ in milliseconds). “Panel C” section provides data on key AP parameters, including resting membrane potential (RMP, in millivolts), maximal rate of AP upstroke velocity (dV/dt_max, in volts per second), AP duration at 20% repolarization (APD₂₀, in milliseconds). Sheet “Panel D” provides additional important AP repolarization data, including AP duration at 90% repolarization (APD₉₀, in milliseconds), short-term variability of APD₉₀ (STV, in milliseconds) at 1 Hz pacing, and the magnitude of APD₉₀ alternans (difference between long and short beats) at 10 Hz pacing (in milliseconds).

Variables

• Action potential duration at 20% repolarization (APD₂₀, in milliseconds)
• Action potential duration at 90% repolarization (APD₉₀, in milliseconds)
• APD₉₀ alternans magnitude (in milliseconds)
• Maximal upstroke velocity (dV/dt_max, in volts per second)
• Resting membrane potential (RMP, in millivolts)
• Short-term variability of APD₉₀ (STV, in milliseconds)

File: Fig4_data_DAD.xlsx

Description: This file contains data on delated afterdepolarizations (DADs) recorded in ventricular cardiomyocytes following cessation of tachypacing (10 Hz) in vehicle-treated wild-type mice (WT+Veh) and in db/db mice with chronic aldosterone infusion (db/db+Aldo) with or without empagliflozin (Empa) in vivo treatment. Sheet “Panel A” provides representative DAD traces (time in milliseconds and membrane voltage in millivolts) and the frequency of DADs (Number of DADs per minute).

Variables

• Delayed afterdepolarization (DAD) frequency (Number of DADs per minute)

File: Fig5_data_IK1_IKv.xlsx

Description: This file contains data on the inward rectifier K⁺ current (I_K1) and the voltage-gated K⁺ currents (I_Kv) in ventricular cardiomyocytes isolated from vehicle-treated wild-type mice (WT+Veh) and db/db mice with chronic aldosterone infusion (db/db+Aldo) with or without empagliflozin (Empa) in vivo treatment. Sheet “Panel A” provides typical I_K1 traces (time in milliseconds and I_K1 density in amperes per farad). Sheet “Panel B” provides data on cell membrane capacitance (in picofarads), inward I_K1 density at -140 millivolts (in amperes per farad), and outward I_K1 density at -40 millivolts (in amperes per farad). Sheet “Panel C” provides typical I_Kv traces (time in milliseconds and I_Kv density in amperes per farad). Sheet “Panel D” provides data on the current density of the transient outward K⁺ current (I_to), the slowly inactivating K⁺ current (I_{K, slow}), and the sustained K⁺ current (I_sus) at +60 millivolts (in amperes per farad). These K⁺ currents were separated by biexponential fitting to I_Kv traces.

Variables

•  Cell membrane capacitance (in picofarads)
• Inward rectifier K⁺ current (I_K1) density at -140 millivolts (in amperes per farad)
• Inward rectifier K⁺ current (I_K1) density at -40 millivolts (in amperes per farad)
• Slowly inactivating K⁺ current (I_{K, slow}) density at +60 millivolts (in amperes per farad)
• Sustained K⁺ current (I_sus) density at +60 millivolts (in amperes per farad)
• Transient outward K⁺ current (I_to) density at +60 millivolts (in amperes per farad)
• Voltage-gated K⁺ current (I_Kv) density (in amperes per farad)

File: Fig6_data_ICa_L_INa_L.xlsx

Description: This file contains data on the L-type Ca²⁺ current (I_Ca,L) and the late Na⁺ current (I_Na,L) in ventricular cardiomyocytes isolated from vehicle-treated wild-type mice (WT+Veh) and db/db mice with chronic aldosterone infusion (db/db+Aldo) with or without empagliflozin (Empa) in vivo treatment. Sheet "Panel A" provides typical I_Ca,L traces (time in milliseconds and I_Ca,L density in amperes per farad), and data on the voltage-dependence of I_Ca,L (current-voltage relationship, I-V, voltage steps are expressed in millivolts, and currents are expressed in amperes per farad), and I_Ca,L density at 0 millivolt (in amperes per farad). Sheet "Panel B" provides typical I_Na,L traces (time in milliseconds and I_Na,L density in amperes per farad) and data on I_Na,L density (in amperes per farad).

Variables

• L-type Ca²⁺ current (I_Ca,L) density (in amperes per farad)
• Late Na⁺ current (I_Na,L) density (in amperes per farad)

File: Fig7_data_CaT.xlsx

Description: This file contains data on ventricular cardiomyocyte intracellular Ca²⁺ transient (CaT) in vehicle-treated wild-type mice (WT+Veh) and in db/db mice with chronic aldosterone infusion (db/db+Aldo) with or without empagliflozin (Empa) in vivo treatment. Sheet “Panel A” provides typical CaT traces (time in milliseconds and Fluo-4 fluorescence expressed as background corrected F/F₀, where F₀ is the non-paced baseline fluorescence) at 1 Hz steady-state pacing. Sheet “Panel B” provides CaT parameters data, including diastolic [Ca^2+^], peak systolic [Ca^2+^], and CaT amplitude (difference between baseline and peak fluorescence, normalized to non-paced F₀). Sheet “Panel C” provides additional intracellular Ca²⁺ handling data, including CaT tau decay (in milliseconds), sarcoplasmic reticulum (SR) Ca²⁺ load assessed by rapid caffeine application (difference between baseline and peak fluorescence, normalized to non-paced F₀), and diastolic Ca²⁺ spark frequency (number of Ca²⁺ sparks per 100 micrometer per second).

Variables

• CaT amplitude (difference between baseline and peak fluorescence, normalized to non-paced F₀)
• CaT tau decay (in milliseconds)
• Sarcoplasmic reticulum (SR) Ca²⁺ load assessed by rapid caffeine application (difference between baseline and peak fluorescence, normalized to non-paced F₀)

File: Fig10_data_Immunoblots.xlsx

Description: This file contains data on the protein expression and phosphorylation state of key Ca handling proteins in the heart, including sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) , Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and phospholamban (PLN), in vehicle-treated wild-type mice (WT+Veh) and in db/db mice with chronic aldosterone infusion (db/db+Aldo) with or without empagliflozin (Empa) in vivo treatment. Sheet “Panel B” provides data on the expression of SERCA2, CaMKII, and its autophosphorylation at threonine 287 (pT287) site. Expression of SERCA2 and CaMKII was assessed relative to GAPDH, and all reported values are normalized to WT+Vehicle. Sheet “Panel D” provided data on the expression and phosphorylation of PLN at serine 16 (pS16) and threonine 17 (pT17) site. Expression of PLN was assessed relative to GAPDH, and all reported values are normalized to WT+Vehicle.

Variables

• SERCA2/GAPDH immunoblot intensity (normalized to WT+Vehicle control)
• CaMKII/GAPDH immunoblot intensity (normalized to WT+Vehicle control)
• pT287 to total CaMKII immunoblot intensity (normalized to WT+Vehicle control)
• PLN/GAPDH immunoblot intensity (normalized to WT+Vehicle control)
• pS16 to total PLN immunoblot intensity (normalized to WT+Vehicle control)
• pT17 to total PLN immunoblot intensity (normalized to WT+Vehicle control)

File: RNAseq.zip

Description: This compressed file contains 7 Excel files with RNA-sequencing data.

"Online Resource 1_HFpEFvsControl_DEGenes.xslx" provides differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice with chronic aldosterone infusion (db/db+Aldo) versus wild-type vehicle controls (WT+Veh) murine hearts. Merged and sex-specific results (“Both sexes”, “Female only”, and “Male only”) are provided in separate sheets.

"Online Resource 2_HFpEF+EMPAvsControl+EMPA_DEGenes.xlsx" provides differentially expressed genes (DEGs) empagliflozin (Empa)-treated leptin receptor-deficient db/db mice with chronic aldosterone infusion (db/db+Aldo) versus wild-type vehicle control (WT+Veh) murine hearts. Merged and sex-specific results (“Both sexes”, “Female only”, and “Male only”) are provided in separate sheets.

"Online Resource 3_DEGenes_comparison_by_condition_sex.xlsx" provides differentially expressed genes (DEGs) in db/db mice with chronic aldosterone infusion (db/db+Aldo) and vehicle-treated wild-type mice (WT+Veh) with or without empagliflozin (Empa) in vivo treatment, and separately in males and females. DEGs in both sexes and sex-differences are shown in separate excel sheets.

"Online Resource 4_GOTerms_by_condition.xlsx" provides Gene Ontology (GO) biological processes in db/db mice with chronic aldosterone infusion (db/db+Aldo) and vehicle-treated wild-type mice (WT+Veh) with or without empagliflozin (Empa) in vivo treatment. Differentially downregulated and upregulated processes between each group are provided in separate excel sheets.

"Online Resource 5_GOTerms_by_sex.xlsx" provides data on sex-specific Gene Ontology (GO) biological processes in db/db mice with chronic aldosterone infusion (db/db+Aldo) and vehicle-treated wild-type mice (WT+Veh) with or without empagliflozin (Empa) in vivo treatment. Differentially downregulated and upregulated processes in male and female animals are provided in separate excel sheets.

"Online Resource 6_kmeanclusters_clusters_allgenes.xlsx" provides data on 5 distinct clusters of genes differentially expressed between control and heart failure with preserved ejection fraction (HFpEF) samples following K-nearest neighbor (KNN) clustering.

"Online Resource 7_GOTerms_cluster3-4.xlsx" provides data on Gene Ontology (GO) biological processes in cluster 3 and 4, identified by K-nearest neighbor (KNN) clustering of differentially expressed genes.

Variables

• Gene ID refers to mouse Ensembl ID
• BaseMean refers to the average RNA count
• log2FoldChange refers to the change in RNA expression relative to its respective control, expressed as log2 value
• lfcSE refers to the standard error of log2FoldChange
• stat refers to the Wald test statistics, the lof2FoldChange divided by lfcSE
• pvalue refers to the exact raw p value
• padj refers to the adjusted p value for false discovery rate
• EntrezID (or GeneID) refers to a unique, stable numerical identifier assigned to genes by the National Center for Biotechnology Information (NCBI)
• Symbol refers to the abbreviation for a specific gene
• Description refers to the full name of each gene

Code/software

Microsoft Excel can be used to view the data files.

Access information

Other publicly accessible locations of the data:

• GEO (accession number: GSE285966)

Data was derived from the following sources:

• N/A