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located in the myocardium of all cardiac chambers and interventricular septum
(7-10% and 18% of ventricular and atrial cardiomyocytes, respectively). They are
coupled to non-WT1-derived cardiomyocytes.
6.1.9.4
ZFPM2 (FOG2) and Thymosin-
4
Regulators of coronary vasculogenesis are also involved in repair of ischemic
heart damage resulting from vascular insufficiency. Coronary vasculogenesis from
epicardium involves ZFPM2, or Friend of GATA2 (FOG2) and VEGF [ 558 ]. 42
Thymosin-
4, a G actin monomer-binding protein, promotes vascularization from
the embryonic epicardium. Thymosin-
β
progenitor cells derived
from quiescent adult epicardial cells and triggers their migration and differentiation
into fibroblasts and smooth myocytes when stimulated by PDGF and TGF
β
4 stimulates TIE2
+
,
and endothelial cells, in response to a combination of VEGF and FGF2 [ 559 ].
Thymosin-
β
4 product of peptidase cleavage, the pro-angiogenic N acetyl seryl-
aspartyl-lysyl-proline (AcSDKP), stimulates differentiation from adult epicardial
cells into endothelial cells.
β
6.1.9.5
Cysteine-Rich LIM-Only Proteins
Smooth muscle
α
-actin exists in cardiomyocyte progenitors. During cardiomyocyte
differentiation,
-actin gene activity is downregulated as soon as rhythmic con-
tractility starts. LIM-only proteins of the CRP family are also called cysteine and
glycine-rich proteins. They support the organization of proteic complexes both in
the cytoplasm and in the nucleus.
Cysteine-rich LIM-only proteins CRP1 and CRP2 are expressed during the de-
velopment of the cardiovascular apparatus. They bridge GATA transcription factor
to serum response factor. The SRF-CRP-GATA complex strongly activates smooth
muscle genes. Together with SRF and GATA proteins, CRP1 and CRP2 facilitate
smooth muscle differentiation. They are able to convert pluripotent fibroblasts into
smooth myocytes. On the other hand, muscle (cardiac) LIM protein CRP3 impedes
this conversion.
The level of CRP2 protein is correlated with smooth muscle gene activity [ 565 ].
Agent CRP2 is a transcription coadaptor that recruits serum response factor
and remodels silent chromatin in adult cardiomyocytes toward smooth muscle
gene activity.
α
42 FOG2( −/− ) hearts are characterized by a thin ventricular myocardium, common atrioventricular
canal, tetralogy of Fallot, and absence of coronary vasculature. Transgenic re-expression of FOG2
in cardiomyocytes leads to coronary vessel development.
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