Expression of bone morphogenetic protein 4 and its receptors in the remodeling heart.

Abstract

AIMS:

Heart failure is associated with activation of fetal gene programs. Bone morphogenetic proteins (BMPs) regulate embryonic development through interaction with BMP receptors (BMPRs) on the cell surface. We investigated if the expression of BMP4 and its receptors BMPR1a and BMPR2 were activated in post-infarction remodeling and heart failure.

MAIN METHODS:

Left ventricular biopsies were taken from explanted hearts of patients with end-stage heart failure due to dilated cardiomyopathy (CMP; n=15) or ischemic heart disease (CAD; n=9), and compared with homograft control preparations from organ donors deceased due to non-cardiac causes (n=7). Other samples were taken from patients undergoing coronary artery bypass grafting (CABG; n=11). Mice were subjected to induced infarction by permanent coronary artery ligation or sham operation, and hearts were sampled serially thereafter (n=7 at each time point).

KEY FINDINGS:

Human and mouse hearts expressed BMP4 and both receptor subtypes. CABG and CMP patients had increased expression of mRNA encoding for BMP4, but unchanged protein. Mouse hearts had increased BMP4 precursor protein 24h after infarction. BMPR1a protein decreased in CAD patients and initially in postinfarcted mouse hearts, but increased again in the latter after two weeks. Human recombinant BMP4 promoted survival after H2O2 injury in HL-1 cells, and also protected adult mouse cardiomyocytes against hypoxia-reoxygenation injury.

SIGNIFICANCE:

Adult hearts express BMP4, the mRNA increasingly so in patients with coronary artery disease with good cardiac function. BMPRs are downregulated in cardiac remodeling and failure. Recombinant BMP4 has protective effects on cultured cardiomyocytes.

• Authors: Xueping Wu, Julia Sagave, Arkady Rutkovskiy, Fred Haugen, Anton Baysa, Ståle Nygård, Gabor Czibik, Christen Peder Dahl, Lars Gullestad, Jarle Vaage, Guro Valen
• Journal: Life sciences (Life Sci) Vol. 97 Issue 2 Pg. 145-54 (Mar 03 2014) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 24398041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Bone Morphogenetic Protein 4
• RNA, Messenger
• Bone Morphogenetic Protein Receptors, Type I
• Bone Morphogenetic Protein Receptors, Type II

Topics

• Adult
• Aged
• Animals
• Bone Morphogenetic Protein 4 (genetics)
• Bone Morphogenetic Protein Receptors, Type I (genetics)
• Bone Morphogenetic Protein Receptors, Type II (genetics)
• Cardiomyopathy, Dilated (physiopathology)
• Coronary Artery Disease (physiopathology)
• Disease Models, Animal
• Down-Regulation
• Female
• Heart Failure (physiopathology)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Myocardial Infarction (physiopathology)
• Myocardial Ischemia (physiopathology)
• Myocytes, Cardiac (pathology)
• RNA, Messenger (metabolism)
• Time Factors
• Ventricular Remodeling
• Young Adult