High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation

Received May 29, 2017; Revised Jul 25, 2017; Accepted Aug 2, 2017

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1. Introduction

Angiopoietin-like 2 (ANGPTL2) belongs to the angiopoietin-like family, a family of eight (ANGPTL1–8) members of glycoproteins [1]. Their structure is similar to that of angiopoietins, and they possess a typical N-terminal coiled-coil domain, a short linker peptide, and a C-terminal fibrinogen-like domain [2]. ANGPTL2 was cloned, expressed, and characterized for the first time in 1999; it is a glycosylated protein of 493 amino acids, of 57 kDa (64 kDa with the glycosylations) [2]. One report proposed that ANGPTL2 could be cleaved into domain fragments by the tolloid-like 1 protease and be inactivated, at least in vitro in cultured cancer cells [3]. It is expressed in many tissues and is secreted in the systemic circulation [2, 4, 5]. Circulating levels of ANGPTL2 in human healthy volunteers range from ~1 to 3 ng/ml [6] (Tables 1, 2, and 3), with similar levels between males and females [5, 7–9]. Higher values are measured in patients with chronic or autoimmune diseases, and discrepancies between circulating levels reported in different studies are most likely due to the differences in age, ethnic background, geographical location, clinical characteristics, and/or severity of the disease and to a lesser extent to the ELISA kit used to quantify ANGPTL2 levels (Tables 1, 2, and 3).

Table 1

Circulating levels of ANGPTL2 in cardiovascular diseases.

Reference	Patients	Serum ANGPTL2 (ng/ml)	ELISA kit	Conclusion of the study
[48]	Chronic kidney disease (stage 5) ± kidney transplant, Canada	from 71 [53–95] to 11 [9–15] after kidney transplant	USCN Life Science Inc., China	High ANGPTL2 after kidney transplant is associated with aortic stiffness, pulse pressure, renal function, and mortality.
[44]	Hisayama study, general population, Japan	Q1: <2.2Q4: >3.4	IBL, Japan	High ANGPTL2 is an independent factor for T2DM development.
[50]	Coronary artery disease versus age-matched controls, Canada	~6.0 versus 1.0 in controls	USCN Life Science Inc.,...