What question did this study set out to answer?

Investigate how dyslipidemia and metabolic distress alter myocardial inflammation and macrophage phenotypes in diastolic dysfunction, and evaluate whether SGLT2 inhibition can mitigate these immune alterations.

December 21, 2023CirculationOpen Access

Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction

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Why the study?

How metabolic changes affect myocardial inflammation in the context of HFpEF is not known.

Does dapagliflozin improve the cardiac immune infiltrate profile in a mouse model of dyslipidemia-induced diastolic dysfunction?

Population

ApoE knockout mice fed a Western diet

Comparison

Dapagliflozin vs vehicle

Design

Randomized preclinical animal study

Follow-up

8 weeks

Authors

CPCristina PanicoHumanitas University AFArianna FelicettaIRCCS Humanitas Research Hospital PKPaolo KunderfrancoIRCCS Humanitas Research Hospital

Discussion

Member takes

Implication

Hypothesis-generating for SGLT2i anti-inflammatory effects in metabolic HFpEF; leaves open human translation.

Key Points

Investigate how dyslipidemia and metabolic distress alter myocardial inflammation and macrophage phenotypes in diastolic dysfunction, and evaluate whether SGLT2 inhibition can mitigate these immune alterations.
Performed single-cell RNA sequencing and bioinformatic profiling on cardiac cells from ApoE knockout mice fed a Western diet to resolve macrophage subpopulations and intercellular signaling networks.
Randomized mice to receive the sodium glucose cotransporter-2 inhibitor dapagliflozin or vehicle for 8 weeks.
Western diet-fed ApoE knockout mice developed impaired diastolic function, diminished exercise capacity, pulmonary congestion, and severe cardiac lipid accumulation.
Single-cell transcriptomics revealed four cardiac macrophage subsets marked by proinflammatory activation driven through endoplasmic reticulum stress pathways, triggering cytokine signaling linked to cardiomyocyte hypertrophy, fibrosis, and autophagy.
Treatment with dapagliflozin conferred a distinct anti-inflammatory effect by ameliorating the pathological cardiac immune infiltrate profile.

Structured PICO

Does dapagliflozin improve the cardiac immune infiltrate profile in a mouse model of dyslipidemia-induced diastolic dysfunction?

Population

ApoE knockout mice fed a Western diet (model of dyslipidemia-induced diastolic dysfunction)

Intervention

Dapagliflozin for 8 weeks

Comparator

Vehicle for 8 weeks

Outcome

Cardiac immune infiltrate profile (macrophage subpopulations and inflammatory gene activation)surrogate

In a mouse model of HFpEF, SGLT2 inhibition with dapagliflozin exerted anti-inflammatory effects on cardiac macrophages, suggesting a potential mechanism for its benefit in metabolic HFpEF.

Cite This Study

Panico et al. (2023) studied this question.

synapsesocial.com/papers/69fe79dfd8476229fea35a70 https://doi.org/10.1161/circulationaha.122.062984

Topics

Lipid management

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Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Single-Cell RNA Sequencing Reveals Metabolic Stress-Dependent Activation of Cardiac Macrophages in a Model of Dyslipidemia-Induced Diastolic Dysfunction

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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