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PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice.


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.

SUBMITTER: Cheng YW 

PROVIDER: S-EPMC8273546 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice.

Cheng Yu-Wen YW   Zhang Ze-Bei ZB   Lan Bei-Di BD   Lan Bei-Di BD   Lin Jing-Rong JR   Chen Xiao-Hui XH   Kong Ling-Ran LR   Xu Lian L   Ruan Cheng-Chao CC   Gao Ping-Jin PJ  

The Journal of experimental medicine 20210708 9


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  ...[more]

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