Lactation Is a Risk Factor of Postpartum Heart Failure in Mice with Cardiomyocyte-specific Apelin Receptor (APJ) Overexpression
Autor: | Kazuya Murata, Juri Hamada, Tomohiro Ishimaru, Junji Ishida, Akiyoshi Fukamizu, Hayase Mizukami, Chiaki Saito |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cardiac function curve medicine.medical_specialty Cardiac fibrosis Cardiomyopathy Cardiomegaly Mice Transgenic 030204 cardiovascular system & hematology Biochemistry Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Pregnancy Internal medicine medicine Animals Humans Lactation Myocytes Cardiac Molecular Biology Apelin receptor Heart Failure Apelin Receptors business.industry Postpartum Period Molecular Bases of Disease Cell Biology medicine.disease Apelin Pleural Effusion 030104 developmental biology Endocrinology Blood pressure Heart failure Female business Postpartum period |
Zdroj: | Journal of Biological Chemistry. 291:11241-11251 |
ISSN: | 0021-9258 |
Popis: | The G protein-coupled receptor APJ and its ligand apelin are highly expressed in cardiovascular tissues and are associated with the regulation of blood pressure and cardiac function. Although accumulating evidence suggests that APJ plays a crucial role in the heart, it remains unclear whether up-regulation of APJ affects cardiac function. Here we generated cardiomyocyte-specific APJ-overexpressing (APJ-TG) mice and investigated the cardiac phenotype in APJ-TG mice. Male and non-pregnant APJ-TG mice showed cardiac hypertrophy, contractile dysfunction, and elevation of B-type natriuretic peptide gene expression in the heart but not cardiac fibrosis and symptoms of heart failure, including breathing abnormality and pleural effusion. We further examined the influence of APJ overexpression in response to physiological stress induced by pregnancy and lactation in the heart. Interestingly, repeating pregnancy and lactation (pregnancy-lactation cycle) exacerbated cardiac hypertrophy and systolic dysfunction and induced cardiac fibrosis, lung congestion, pleural effusion, and abnormal breathing in APJ-TG mice. These data indicate that female APJ-TG mice develop postpartum cardiomyopathy. We showed that lactation, but not parturition, was critical for the onset of postpartum cardiomyopathy in APJ-TG mice. Furthermore, we found that lactating APJ-TG mice showed impaired myocardial angiogenesis and imbalance of pro- and antiangiogenic gene expression in the heart. These results demonstrate that overexpression of APJ in cardiomyocytes has adverse effects on cardiac function in male and non-pregnant mice and that lactation contributes to the development of postpartum cardiomyopathy in the heart with APJ overexpression. |
Databáze: | OpenAIRE |
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