Regional expression of adipogenic-related genes in a
RA, an AAR and the AON.
To evaluate RNA expression in
the LV wall of the IRI model in detail at 2 h after LAD ligation,
a set of TFs related to adipogenesis was examined by
qRT-PCR for each area consisting of the area of necrosis
(AON), an area at risk (AAR) and a remote area (RA), which
were defined by double staining with 2,3,5-triphenyltetrazo-
lium chloride (TTC) and Evans blue (Figure 7a).
Klf4
expression significantly increased in the AON, and
c-Myc
expression significantly increased in all areas over time. The
first wave of TFs (C/Ebp
β
and C/Ebp
δ
) for adipogenesis was
significantly raised in all areas. In contrast, expression of the
second wave of TFs (
Ppar
γ
2
, and
C/Ebp
α
) did not differ in
AON and AAR compared with that in RA. Comparison of
gene expression among areas revealed that
Klf4
expression
in AON was significantly higher than that in RA, and
c-Fos
,
c-Jun,
and
c-Myc
expression levels in AON and AAR were
significantly higher than those in RA. The gene expression of
the first wave of TFs in AON was significantly higher than that in
RA, and the gene expression of the second wave of TFs was
not significantly different among the three areas. The surrogate
TFs (
c-Fos
and
c-Jun
) showed significantly increased expres-
sion in AON and AAR compared with that in RA, which was the
same tendency as that observed for
Klf4
,
c-Myc
,
C/Ebp
β
and
C/Ebp
δ
, suggesting that adipogenesis might be initiated via KM
induction in this cardiac IRI model (Figure 7b).
Figure 3
Global gene expression of OSKM-transduced CMPs. (
a
) Hierarchical clustering analysis of OSKM-transduced CMPs on each day by NIA array analysis. CMP cntrl
indicates untreated CMPs. (
b
) PCA by NIA array analysis. CMPs are categorized based on the principal component 1 (PC1) direction (left). A total of 4577 probes were in the
positive direction on PC1, indicating decreased expression over time, and 5314 probes were in the negative direction of PC1, indicating increased expression over time. (
c
) Genes
in the PC1-positive and -negative directions were categorized based on biological processes using GO annotations (white bars) and KEGG pathways (gray bars)
Cardiac adiposity is regulated by
Klf4
and
c-Myc
D Kami
et al
5
Cell Death and Disease
