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Updated: May 13, 2026
A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction
Published on: March 29, 2024
Comparative effects of statins on murine cardiac gene expression profiles in normal mice
Masafumi Kumazaki1, Hitoshi Ando, Kentarou Ushijima
1Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
Abstract:
Recent clinical data suggest that the efficacy of statin treatment in patients with heart failure varies depending on the drugs administered. The present study was undertaken to compare murine cardiac gene expression profiles following treatment with four different statins. In normal male C57BL/6J mice, 4 weeks of treatment with or without a statin (pitavastatin, pravastatin, rosuvastatin, or atorvastatin) did not affect any biochemical parameters, including the lipid profile. However, cardiac gene expression profiling by microarray analysis revealed distinct patterns among the five groups. Several genes that might be involved in cardiac function, including Ccnd2, Klf7 and Timp3, were differentially regulated by treatment with a specific statin. In the primary cultured neonatal mouse cardiomyocytes, statin-induced changes in the expression of these genes were largely unaffected by supplementation with mevalonic acid. These data indicate that statins directly regulate cardiac gene expression in a drug-specific manner in normal mice. Additional studies are needed to determine whether these differences influence the clinical efficacy in particular patients, such as those with heart failure.
Insights
Different statins impact cardiac gene expression uniquely in mice, independent of lipid levels. This drug-specific regulation suggests potential variations in clinical efficacy for heart failure patients.
Area of Science:
- Cardiovascular Pharmacology
- Molecular Cardiology
- Genomics
Background:
- Clinical data indicate variable statin efficacy in heart failure patients.
- The specific mechanisms underlying these differences remain unclear.
Purpose of the Study:
- To compare cardiac gene expression profiles in mice treated with four distinct statins.
- To investigate whether statins directly modulate cardiac gene expression in a drug-specific manner.
Main Methods:
- Murine model using C57BL/6J mice treated with pitavastatin, pravastatin, rosuvastatin, or atorvastatin for 4 weeks.
- Biochemical parameter analysis, including lipid profiles.
- Cardiac gene expression profiling using microarray analysis.
- In vitro studies using primary cultured neonatal mouse cardiomyocytes.
Main Results:
- Statin treatment did not alter biochemical parameters or lipid profiles in normal mice.
- Microarray analysis revealed distinct cardiac gene expression patterns among the different statin treatment groups.
- Specific genes (Ccnd2, Klf7, Timp3) involved in cardiac function were differentially regulated by individual statins.
- Statin-induced gene expression changes in cardiomyocytes were largely independent of mevalonic acid supplementation.
Conclusions:
- Statins directly regulate cardiac gene expression in a drug-specific manner in normal mice.
- These findings suggest that the observed differences in gene regulation may contribute to variable clinical efficacy of statins, particularly in heart failure patients.
