October 1, 2019Pulmonary CirculationOpen Access

Natriuretic peptide receptor C contributes to disproportionate right ventricular hypertrophy in a rodent model of obesity‐induced heart failure with preserved ejection fraction with pulmonary hypertension

Q: What is the clinical evidence from this study?

Study design: Other. Population: Obesity-induced heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension (n=96). Intervention: High fat diet (60% fat) and NPRC overexpression vs. Nutrient matched control diet and empty vector. Primary outcome: Development of right ventricular dysfunction, pulmonary hypertension, and HFpEF, and NPRC expression.

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Key result

In a rodent model of obesity-induced HFpEF, upregulation of natriuretic peptide receptor C (NPRC) contributed to disproportionate right ventricular remodeling by increasing cardiomyocyte hypertrophy.

Why the study?

HFpEF has no therapies that improve mortality, and an animal model of obesity-induced HFpEF with pulmonary hypertension was evaluated to gain insight into the pathogenesis of right ventricular failure.

Population

Two strains of mice (AKR and C3H) and H9C2 cells

Comparison

High fat (60% fat) vs control diet

Design

Preclinical animal and in vitro study

Follow-up

Up to 20 weeks

Authors

VAVineet AgrawalVanderbilt University NFNiki FortuneVanderbilt University Medical Center SYSheeline YuYale University

Discussion

Member takes

Implication

Animal models of obesity-induced HFpEF may enable mechanistic RV studies; leaves open translation to human therapies.

Structured PICO

Population

Male AKR and C3H mice evaluated at 0, 2, and 20 weeks on a high-fat or control diet to study obesity-induced HFpEF and pulmonary hypertension.

Intervention

High fat diet (60% lard) for 0, 2, or 20 weeks; in vitro overexpression of NPRC.

Comparator

Nutrient matched control diet; in vitro empty vector.

Outcome

Development of right ventricular dysfunction, pulmonary hypertension, and HFpEF assessed by echocardiography, cardiac catheterization, histology, and RNA sequencing.surrogate

NPRC contributes to right ventricular remodeling in obesity-induced pulmonary hypertension-HFpEF by increasing cardiomyocyte hypertrophy, representing a potential therapeutic target.

Limitations

The two mouse strains differ genetically in a number of ways, meaning the contribution of other gene pathways cannot be ruled out.
The study specifically used male mice, so it is unclear whether these findings apply to female mice.
In vitro studies focused on cardiomyoblast cells, but NPRC could be exerting a pro-hypertrophic effect through non-cardiomyocyte cells in vivo.
It is not clear mechanistically whether the effect is due to NPRC competing for endogenous natriuretic peptides or directly resulting from signaling downstream of NPRC.
Underpowered to detect smaller early differences in pulmonary vascular remodeling based on numbers of animals per group
Differences in the compositions of control diets compared to previous studies may account for early changes

Cite This Study

Agrawal et al. (2019) studied Obesity-induced heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension (n=96). High fat diet (60% fat) and NPRC overexpression vs. Nutrient matched control diet and empty vector was evaluated on Development of right ventricular dysfunction, pulmonary hypertension, and HFpEF, and NPRC expression. In a rodent model of obesity-induced HFpEF, upregulation of natriuretic peptide receptor C (NPRC) contributed to disproportionate right ventricular remodeling by increasing cardiomyocyte hypertrophy.

synapsesocial.com/papers/6a8b068ef71fc1553cbe984a https://doi.org/10.1177/2045894019895452

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Natriuretic peptide receptor C contributes to disproportionate right ventricular hypertrophy in a rodent model of obesity‐induced heart failure with preserved ejection fraction with pulmonary hypertension

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Natriuretic peptide receptor C contributes to disproportionate right ventricular hypertrophy in a rodent model of obesity‐induced heart failure with preserved ejection fraction with pulmonary hypertension

Discussion

Member takes

Implication

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider