Angiopoietin-like protein 7: A narrative review and its potential roles in post-myocardial infarction fibrosis

Figures

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  Figure 1. Schematic representation of the structural domains, post-translational modifications, and oligomerization of ANGPTL7 The ANGPTL7 monomer consists of an N-terminal signal peptide, a coiled-coil domain, and a C-terminal FLD. During maturation, the signal peptide is cleaved, and the protein undergoes N-linked glycosylation. Subsequently, mature monomers assemble into higher-order oligomers through interchain disulfide bonds formed via cysteine residues (e.g., cys-53) within the coiled-coil domain. ANGPTL7, angiopoietin-like protein 7; ECM, extracellular matrix; FLD, fibrinogen-like domain. This figure was created by Figdraw (https://www.figdraw.com/).

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  Figure 2. The core molecular mechanisms of ANGPTL7 in different pathologies These mechanisms can be broadly categorized as direct pro-fibrotic effects, where ANGPTL7 directly remodels the ECM and activates key fibrotic signaling pathways, including the TGF-β and RhoA/ROCK pathways, leading to cellular stiffening and pathological matrix deposition; indirect pro-fibrotic effects, mediated by its ability to amplify inflammation and oxidative stress. ANGPTL7 activates pro-inflammatory pathways such as p38 MAPK and NF-κB, while also exhibiting a complex, dual immunomodulatory role by binding to the inhibitory receptor LILRB2 on myeloid cells; crosstalk with other key pathways, highlighting its ability to interact with other critical signaling systems such as Wnt/β-catenin, insulin signaling (via SOCS3), and angiogenesis, thereby further influencing cellular behavior and tissue remodeling in a context-dependent manner. ANGPTL7, angiopoietin-like protein 7; Akt, protein kinase B; CLANs, cross-linked actin networks; COX-2, cyclooxygenase-2; ECM, extracellular matrix; eNOS, endothelial nitric oxide synthase; FLD, fibrinogen-like domain; HO-1, heme oxygenase-1; ICAM-1, intercellular adhesion…

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  Figure 3. The involvement of ANGPTL7 in the pathogenesis of cardiovascular diseases In atherosclerosis, ANGPTL7 acts as an amplifier of vascular inflammation and endothelial dysfunction by inducing oxidative stress and upregulating adhesion molecules (e.g., ICAM-1 and VCAM-1). It is also implicated in regulating adaptive immune responses and has been linked to ferroptosis within atherosclerotic plaques. In hypertension, ANGPTL7 is a downstream effector of AngII. The AngII-ANGPTL7 axis promotes VSMC proliferation and inflammation, contributing to pathological vascular remodeling and increased arterial stiffness. In heart failure, elevated circulating levels of ANGPTL7 have been identified as a strong and independent prognostic biomarker for short-term mortality in patients with AHF, likely reflecting its active involvement in adverse myocardial remodeling through its pro-fibrotic and pro-inflammatory functions.AHF, acute heart failure; AngII, angiotensin II; ANGPTL7, angiopoietin-like protein 7; ICAM-1, intercellular adhesion molecule 1; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NT-proBNP, N-terminal pro-B-type natriuretic peptide; VCAM-1, vascular cell adhesion…