Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction

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.