Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction.

Abstract

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.

• Authors: Zhe Tian, Keishi Miyata, Jun Morinaga, Haruki Horiguchi, Tsuyoshi Kadomatsu, Motoyoshi Endo, Jiabin Zhao, Shunshun Zhu, Taichi Sugizaki, Michio Sato, Kazutoyo Terada, Takahiro Okumura, Toyoaki Murohara, Yuichi Oike
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 82 Issue 2 Pg. 437-447 (01 25 2018) ISSN: 1347-4820 [Electronic] Japan
• PMID: 28890470 (Publication Type: Journal Article)

Chemical References

• ANGPTL2 protein, human
• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angptl2 protein, mouse

Topics

• Adult
• Aged
• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins (blood)
• Animals
• Cardiomyopathy, Dilated (blood)
• Female
• Heart Diseases (blood)
• Heart Failure (blood, prevention & control)
• Humans
• Keratinocytes (chemistry)
• Male
• Mice
• Mice, Transgenic
• Middle Aged
• Myocytes, Cardiac (metabolism)