Fibronectin is essential for reparative cardiac progenitor cell response after myocardial infarction.

Abstract:

RATIONALE:Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application, despite limited mechanistic understanding of the endogenous response after myocardial infarction (MI). Extracellular matrix undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair. OBJECTIVE:To demonstrate the significance of fibronectin (Fn), a component of the extracellular matrix, for induction of the endogenous CPC response to MI. METHODS AND RESULTS:This report shows that presence of CPCs correlates with the expression of Fn during cardiac development and after MI. In vivo, genetic conditional ablation of Fn blunts CPC response measured 7 days after MI through reduced proliferation and diminished survival. Attenuated vasculogenesis and cardiogenesis during recovery were evident at the end of a 12-week follow-up period. Impaired CPC-dependent reparative remodeling ultimately leads to continuous decline of cardiac function in Fn knockout animals. In vitro, Fn protects and induces proliferation of CPCs via β₁-integrin-focal adhesion kinase-signal transducer and activator of transcription 3-Pim1 independent of Akt. CONCLUSIONS:Fn is essential for endogenous CPC expansion and repair required for stabilization of cardiac function after MI.

journal_name

Circ Res

journal_title

Circulation research

authors

Konstandin MH,Toko H,Gastelum GM,Quijada P,De La Torre A,Quintana M,Collins B,Din S,Avitabile D,Völkers M,Gude N,Fässler R,Sussman MA

doi

10.1161/CIRCRESAHA.113.301152

subject

Has Abstract

pub_date

2013-07-05 00:00:00

pages

115-25

issue

2

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.113.301152

journal_volume

113

pub_type

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