Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 694

(diastole; i.e., (sarco(endo)plasmic reticulum Ca 2 + ATPase SERCA2a, phospho-
lamban, and S100 Ca 2 + -binding protein S100a1) [ 1424 ]. 18
A combination of 3 transcription factors, GATA4, myocyte enhancer factor
MEF2c, and T-box factor Tbx5, reprograms fibroblasts into functional cardiomy-
ocytes in vitro. Transfer of the Tbx5 gene using viral vector can convert cardiac
fibroblasts from the infarct region into cardiomyocyte-like cells [ 1426 ].
Sonic Hedgehog 19 (Shh; Vol. 3 - Chap. 10. Morphogen Receptors) that regulates
heart development during embryogenesis, can preserve, after intramyocardial gene
transfer in adult animal hearts, the left ventricular function after both acute and
chronic myocardial ischemia by enhanced neovascularization, as well as reduced
fibrosis and apoptosis [ 1427 ].

11.4.3 Tissue Engineering

Tissue engineering 20 is the construction of living tissue. Bioreactors are devices
used for the growth of tissues in an artificial environment that mimicks the
physiological conditions.
In vivo biomechanical 21 and chemicophysical conditions that mimic the natural
environment (mechanical loading such as flow in particular) are created for in
vitro cell conditioning and construction of blood vessel, heart valves, etc., with
features similar to the native tissue ones. Mechanical loading with a conditioning
protocol (cycle frequency and magnitude range) of tissue in formation in bioreactors

18 The amplitude and frequency of Ca 2 + transients are regulated by the phosphorylation of
Ca 2 + regulators, which depends on the balance between the activity of kinases, such as PKA
and CamK2, and phosphatases, such as PP1 and PP2. Protein kinase-A, an amplifier of

β

-
adrenergic receptor signaling, phosphorylates (activates) Ca V 1.2 channels and ryanodine receptors
as well as (inactivates) phospholamban, hence raising SERCA activity, in addition to (activates)
PP1 r1a , PP1 r1b , and PP1 r2 , converting them in potent inhibitors of protein phosphatase-1. Cardiac-
specific Ca 2 + sensor S100a1 is preferentially produced and abounds in the heart; it is the
predominant subtype among other S100 isoforms, such as S100a4, S100a6, and S100b. It
lodges mainly in ventriculomyocytes. It localizes to the sarcoplasmic reticulum, sarcomere, and
mitochondria. It interacts in a Ca 2 + -dependent manner with the cardiac ryanodine receptor RyR2
(augmented cytosolic Ca 2 + transients), the SERCA2a-phospholamban complex (increased Ca 2 +
resequestration), titin, and mitochondrial F 1 ATPase (enhanced ATP generation) [ 1425 ]. Its nitric
oxide-dependent S-glutathionylation increases its Ca 2 + affinity (nanomolar range). Therefore, it is
an inotropic and lusitropic enhancer.
19 Sonic Hedgehog is a member of the Hedgehog family of secreted glycoproteins. It acts
via Patched-1-Smoothened receptor complex to upregulate the transcription of zinc finger Gli
transcription factor.
20 Tissue engineering is a multidisciplinary topic that involves, in particular, cell and molecular
biologists, biomaterial scientists, and imaging specialists to develop materials that can replace or
support diseased or damaged tissues and restore or improve tissue functions.
21 Because mechanical forces regulate the physiological functioning of the cells, these influences
must be reproduced in cell and tissue engineering.