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A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure
Published on: April 30, 2020
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Midkine exacerbates pressure overload-induced cardiac remodeling
Shunsuke Netsu1, Tetsuro Shishido1, Tatsuro Kitahara1
1Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
Biochemical and Biophysical Research Communications
|December 3, 2013
Summary
Midkine exacerbates heart failure by promoting cardiac hypertrophy and dysfunction. Overexpressing midkine in the heart worsened outcomes after transverse aortic constriction surgery in mice.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Growth Factor Signaling
Background:
- Midkine is a growth factor linked to heart failure severity.
- Its precise role in heart failure pathogenesis requires further investigation.
Purpose of the Study:
- To elucidate the role of midkine in the development of heart failure.
- To investigate the impact of midkine on cardiac hypertrophy and remodeling.
Main Methods:
- Utilized a mouse model of transverse aortic constriction (TAC) surgery.
- Generated transgenic mice with cardiac-specific midkine overexpression (MK-Tg) and compared them to wild-type (WT) mice.
- Assessed cardiac function, hypertrophy markers, and survival rates post-TAC.
Main Results:
- Midkine expression increased in kidneys and lungs post-TAC, but not significantly in the heart.
- Cardiac-specific midkine overexpression in MK-Tg mice led to increased phosphorylation of ERK1/2 and AKT.
- MK-Tg mice exhibited exacerbated cardiac hypertrophy, dysfunction, and reduced survival rates after TAC compared to WT mice.
Conclusions:
- Midkine plays a critical role in mediating cardiac hypertrophy and adverse remodeling in heart failure.
- Targeting midkine may offer a therapeutic strategy for heart failure.
Keywords:
ANPBNPCTGFCardio–renal interactionERKGAPDHHeart failureMHCMidkinePI3KTACatrial natriuretic peptidebrain natriuretic peptideconnective tissue growth factorextracellular signal-regulated kinaseglyceraldehyde 3-phosphate dehydrogenasemyosin heavy chainphosphatidylinositol 3-kinasetransverse aortic constriction
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