Affiliation:
1. From the Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.
Abstract
Background—
We hypothesized that c-kit receptor function in the bone marrow is important for facilitating healing, leading to efficient cardiac repair after myocardial infarction (MI).
Methods and Results—
We used
Kit
W
/Kit
W-v
c-kit mutant mice and their wild-type littermates to assess the importance of c-kit function in cardiac remodeling after coronary ligation. We found that mutant mice developed 1.6-fold greater ventricular dilation (
P
=0.008) attributable to a 1.3-fold greater infarct expansion by day 14 after MI (
P
=0.01). The number of proliferating smooth muscle α-actin expressing cells was 1.8-fold lower in mutant mice at day 3 (
P
<0.01), resulting in a 1.6 to 1.8-fold reduction in total regional nonvascular smooth muscle α-actin expressing cells by both microscopy and flow cytometry (
P
<0.001 for both). This decrease was accompanied by a 1.4-fold reduction in the number of CD31 expressing blood vessels (
P
<0.05). Prior transplantation of wild-type bone marrow cells into mutant mice rescued the efficient establishment of vessel-rich repair tissue by inducing a 1.5-fold increase in nonvascular smooth muscle α-actin expressing cells and CD31 expressing blood vessels (
P
<0.05 for both). The increased recruitment of cells into the infarct region in the chimeric mice was associated with reduced infarct expansion (
P
<0.03) compared to wild-type levels.
Conclusions—
Bone marrow c-kit function critically impacts the myofibroblast repair response in infarcted hearts. Interventions that increase the infiltration of c-kit
+
cells to the infarcted heart may potentiate this endogenous repair response, prevent infarct expansion, and improve the recovery of cardiac function after MI.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
62 articles.
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