PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice.
J Exp Med
; 218(9)2021 09 06.
Article
in En
| MEDLINE
| ID: mdl-34236404
ABSTRACT
Obesity-induced secretory disorder of adipose tissue-derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)-infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow-specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Platelet-Derived Growth Factor
/
Urokinase-Type Plasminogen Activator
/
Lymphokines
/
Ventricular Remodeling
/
Obesity
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2021
Document type:
Article
Affiliation country:
China