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Updated: Aug 13, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction
Zhe Tian1, Keishi Miyata1,2, Jun Morinaga1
1Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University.
Background:
Recently, it was reported that angiopoietin-like protein 2 (ANGPTL2) secreted from a pathologically stressed heart accelerates cardiac dysfunction in an autocrine/paracrine manner, and that suppression of ANGPTL2 production in the heart restored cardiac function and myocardial energy metabolism, thereby blocking heart failure (HF) development. Interestingly, circulating ANGPTL2 concentrations reportedly increase in HF patients, suggesting a possible endocrine effect on cardiac dysfunction. However, it remains unclear why circulating ANGPTL2 increases in those subjects and whether circulating ANGPTL2 alters cardiac function in an endocrine manner.
Methods And Results:
It was found that circulating ANGPTL2 levels are positively correlated with left atrial diameter and pulmonary capillary wedge pressure, and are inversely proportional to the percent of ejection fraction in patients with dilated cardiomyopathy. Furthermore, in mice, circulating ANGPTL2 concentrations increased as HF developed following transverse aorta constriction (TAC), and were inversely correlated with the percent of fractional shortening. Interestingly, although circulating ANGPTL2 concentrations significantly increased in transgenic mice overexpressing keratinocyte-derived ANGPTL2, no pathological cardiac remodeling was seen. Furthermore, it was observed that there was no difference in HF development between transgenic mice and controls following TAC surgery.
Conclusions:
Circulating ANGPTL2 levels increase in subjects experiencing cardiac dysfunction. However, circulating ANGPTL2 does not promote cardiac dysfunction in an endocrine manner, and increased levels of circulating ANGPTL2 seen during HF are a secondary effect of increased ANGPTL2 secretion from stressed hearts in HF pathologies.
Insights
Increased circulating angiopoietin-like protein 2 (ANGPTL2) does not cause heart failure (HF) in an endocrine manner. Elevated ANGPTL2 levels in HF patients are a secondary effect of cardiac stress.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Angiopoietin-like protein 2 (ANGPTL2) from stressed hearts accelerates cardiac dysfunction.
- Elevated circulating ANGPTL2 in heart failure (HF) suggests a potential endocrine role.
- The source and endocrine impact of increased circulating ANGPTL2 in HF remain unclear.
Purpose of the Study:
- To investigate the endocrine role of circulating ANGPTL2 in heart dysfunction.
- To determine the cause of increased circulating ANGPTL2 in HF patients.
Main Methods:
- Correlated circulating ANGPTL2 with cardiac parameters in dilated cardiomyopathy patients.
- Measured circulating ANGPTL2 in mice with transverse aorta constriction (TAC)-induced HF.
- Assessed cardiac remodeling in transgenic mice overexpressing keratinocyte-derived ANGPTL2.
Main Results:
- Circulating ANGPTL2 positively correlated with left atrial diameter and pulmonary capillary wedge pressure, and inversely with ejection fraction.
- ANGPTL2 levels increased with HF development in mice and inversely correlated with fractional shortening.
- Overexpression of keratinocyte-derived ANGPTL2 did not cause cardiac remodeling or worsen HF post-TAC.
Conclusions:
- Circulating ANGPTL2 levels rise in cardiac dysfunction but do not promote it endocrinely.
- Increased circulating ANGPTL2 in HF is a secondary consequence of cardiac ANGPTL2 secretion.
- ANGPTL2's role in HF appears primarily autocrine/paracrine rather than endocrine.
