In response to myocardial infarction (MI), quiescent cardiac fibroblasts differentiate into myofibroblasts mediating tissue repair in the infarcted area. One of the most widely accepted markers of myofibroblast differentiation is the expression of
Acta2
which encodes smooth muscle alpha-actin (SMαA) that is assembled into stress fibers. However, the requirement of
Acta2
/ SMαA in the myofibroblast differentiation of cardiac fibroblasts and its role in post-MI cardiac repair remained largely unknown. To answer these questions, we generated a tamoxifen-inducible cardiac fibroblast-specific
Acta2
knockout mouse line. Surprisingly, mice that lacked
Acta2
in cardiac fibroblasts had a normal survival rate after MI. Moreover,
Acta2
deletion did not affect the function or overall histology of infarcted hearts. No difference was detected in the proliferation, migration, or contractility between WT and
Acta2
-null cardiac myofibroblasts. It was identified that
Acta2
-null cardiac myofibroblasts had a normal total filamentous actin level and total actin level.
Acta2
deletion caused a unique compensatory increase in the transcription level of
Actg2
and an increase in the protein level of sarcomeric actin isoform(s). In addition, the specific muscle actin isoforms that were upregulated in
Acta2
-null cardiac myofibroblasts varied between individual cells. Moreover, the formation of stress fibers by cytoplasmic actin isoforms, especially the cytoplasmic gamma-actin, was enhanced in
Acta2
-null cardiac myofibroblasts despite their unchanged RNA and protein expression. In conclusion, the deletion of
Acta2
does not prevent the myofibroblast differentiation of cardiac fibroblasts or affect the post-MI cardiac repair, and the increased expression and stress fiber formation of non-SMαA actin isoforms and the functional redundancy between actin isoforms are able to compensate for the loss of
Acta2
in cardiac myofibroblasts.
Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation
