Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 240

phosphocreatine concentration and elevated AMP level activate AMP-activated
protein kinase that increases glucose transport and activates phosphofructokinase
for glycolysis. In the heart, AMPK stimulates 6-phosphofructo 2-kinase activity and
glucose transporter GluT4 expression.
AMP-activated protein kinase also activates mitochondrial estrogen-related
receptor ERR α (or nuclear receptor NR3b1) and peroxisome proliferator-activated

receptor- γ (or NR1c3) coactivator PGC1 α .ERR α ,ERR β (NR3b2), and ERR γ

(NR3b3) regulate cardiac energy metabolism. ERR α interacts with PGC1 α . Fatty

acid oxidation is regulated by PPARs and their coactivator PGC1 α .Thecomplex

formed by ERR targets a set of genes that encode proteins involved

in energy production that results from oxidative phosphorylation (e.g., fatty acid
and glucose uptake, tricarboxylic acid cycle, and electron transport chain) and
transfer (e.g., mitochondrial creatine kinase and adenine nucleotide transporter).
Factor PGC1

α and PGC1 α

stimulates mitochondrial genesis, as it increases the production of
nuclear respiratory factor NRF1 and NRF2 that regulate mitochondrial transcription
factor-A TFAm and ERR

α

(NR3B1) that coordinate the expression of genes
encoding mitochondrial proteins. Moreover, PGC1

α

regulates the expression of
genes encoding proteins involved in fatty-acid oxidation via coactivation of PPAR

α

α

and ERR α .

5.8 Cardiomyocyte Adaptive Growth

Developmental growth deals with normal growth of the heart after birth. Cardiac
hypertrophy is defined by an increase in size of cardiomyocytes. The heart is
capable of acute and chronic hypertrophy . In response to long-term regular exercise
and pregnancy, the heart undergoes physiological growth, or adaptive hypertrophy.
Cardiomyocyte size increase in response to a hypertrophic stimulus is associated
with augmented sarcomerogenesis and expression of natriuretic peptides. The car-
diomyocyte length elevation is larger than the width rise. Both developmental
growth and physiological hypertrophy are characterized by coordinated myocardial
growth matched with heart chamber size, normal organization of sarcomeres, and
enhanced cardiac function.
Myocardial hypertrophy can be either adaptive or maladaptive according to
cardiomyocyte contractility, the former being associated with normal or even
improved function, and the latter with impaired contractile function. Maladaptive
hypertrophy is induced by long-term sustained cardiac stresses and diseases such
as systemic arterial hyperpressure and aortic valve stenosis. Remodeling leads to
a greater increase in cardiomyocyte width than length. Maladaptive hypertrophy is
defined by a myocardial dysfunction.
Increase in the number of cardiomyocytes means hyperplasia . Hyperplasia is
characterized by an increased myocardial dry mass, normal cardiomyocyte size, and
the absence of an abnormal myocardial component.