Multiparity induces persistent myocardial structural, functional and transcriptomic remodelling in mice
Ruth R Magaye1,2, Bing H Wang1,2,3, Hongyi R Liu1
1Heart Failure Research Group, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia.
Multiple pregnancies may increase heart failure risk by causing lasting changes in heart muscle. This study found that multiparous mice showed persistent cardiac remodeling and altered gene expression, suggesting a link to heart failure with preserved ejection fraction (HFpEF).
Area of Science:
- Cardiology
- Reproductive Biology
- Genomics
Background:
- Pregnancy imposes significant hemodynamic and metabolic stress on the heart.
- Multiple pregnancies are linked to an increased risk of heart failure with preserved ejection fraction (HFpEF) later in life.
- The underlying mechanisms connecting multiparity to HFpEF remain largely unknown.
Purpose of the Study:
- To investigate whether repetitive pregnancies cause persistent myocardial remodeling.
- To explore the potential link between multiparity-induced cardiac changes and HFpEF development.
- To identify molecular and structural alterations in the heart associated with multiple pregnancies.
Main Methods:
- Comparison of multiparous (MP) and non-parous (NP) aged mice (C57Bl/6J).
- Assessment of cardiovascular parameters including blood pressure, body composition, cardiac structure, and function via echocardiography.
- Transcriptomic analysis (mRNA levels and RNA sequencing) of left ventricular myocardium.
Main Results:
- MP mice exhibited increased heart-to-tibial length ratio, body weight, and fat mass compared to NP mice.
- MP mice showed impaired cardiac diastolic function (increased isovolumetric relaxation time) and mildly reduced ejection fraction.
- Elevated cardiac marker mRNA (Myh6, Nppa), increased Il18 and fibronectin mRNA, and significant interstitial fibrosis were observed in MP mice.
- RNA sequencing revealed persistent differential expression of 128 genes, with affected pathways including extracellular matrix regulation and organic anion/ion transport.
Conclusions:
- Multiparity induces lasting alterations in cardiac gene expression and myocardial structure that persist into later life.
- These persistent changes provide a potential substrate for the development of heart failure phenotypes, such as HFpEF.
- Further research is needed to elucidate the interaction between pregnancy-associated cardiac remodeling and other HFpEF risk factors.
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