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Deletion of Microfibrillar‐Associated Protein 4 Attenuates Left Ventricular Remodeling and Dysfunction in Heart Failure
- Source :
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- Background Cardiac remodeling predisposes individuals to heart failure if the burden is not solved, and heart failure is a growing cause of morbidity and mortality worldwide. The cardiac extracellular matrix not only provides structural support, but also is a core aspect of the myocardial response to various biomechanical stresses and heart failure. MFAP4 (microfibrillar‐associated protein 4) is an integrin ligand located in the extracellular matrix, whose biological functions in the heart remain poorly understood. In the current study we aimed to test the role of MFAP4 in cardiac remodeling. Methods and Results MFAP4‐deficient (MFAP4 −/− ) and wild‐type mice were subjected to aortic banding surgery and isoproterenol to establish models of cardiac remodeling. We also evaluated the functional effects of MFAP4 on cardiac hypertrophy, fibrosis, and cardiac electrical remodeling. The expression of MFAP4 was increased in the animal cardiac remodeling models induced by pressure overload and isoproterenol. After challenge of 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol, MFAP4 −/− mice exhibited lower levels of cardiac fibrosis and fewer ventricular arrhythmias than wild‐type mice. However, there was no significant effect on cardiomyocyte hypertrophy. In addition, there was no significant difference in cardiac fibrosis severity, hypertrophy, or ventricular arrhythmia incidence between wild‐type‐sham and knockout‐sham mice. Conclusions These findings are the first to demonstrate that MFAP4 deficiency inhibits cardiac fibrosis and ventricular arrhythmias after challenge with 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol but does not significantly affect the hypertrophy response. In addition, MFAP4 deficiency had no significant effect on cardiac fibrosis, hypertrophy, or ventricular arrhythmia in the sham group in this study.
- Subjects :
- medicine.medical_specialty
Cardiomyopathy
Cardiomegaly
030204 cardiovascular system & hematology
extracellular matrix proteins
Extracellular matrix
Mice
Ventricular Dysfunction, Left
03 medical and health sciences
0302 clinical medicine
microfibrillar-associated protein 4
Internal medicine
Animals
Medicine
Ventricular remodeling
Aorta
Original Research
Glycoproteins
030304 developmental biology
Heart Failure
Mice, Knockout
Pressure overload
0303 health sciences
Ventricular Remodeling
business.industry
Myocardium
Isoproterenol
pressure overload
Adrenergic beta-Agonists
medicine.disease
Fibrosis
Remodeling
Biomechanical Phenomena
Extracellular Matrix
Disease Models, Animal
Case-Control Studies
Heart failure
cardiovascular system
Cardiology
cardiac remodeling
Carrier Proteins
Cardiology and Cardiovascular Medicine
business
Injections, Intraperitoneal
Signal Transduction
Subjects
Details
- ISSN :
- 20479980
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of the American Heart Association
- Accession number :
- edsair.doi.dedup.....c791271813bcd9ab39e3ed8af6293ff2