Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 238

In addition, CNP prevents proliferation of cardiomyocytes. It also impedes
vasoconstriction caused by angiotensin-1, but not that of angiotensin-2, as it may
be a local regulator of vascular angiotensin-converting enzyme [ 402 ].

5.6.1.8 D-Type Natriuretic Peptides

D-Type (or Dendroaspis) natriuretic peptide (DNP) is derived from the venom
of Dendroaspis augusticeps (green Mamba snake). The 38-amino acid peptide
DNP can be detected in human plasma (average concentration

6 pg/ml [range
2-100 pg/ml]) [ 402 ]. It can be identified in the atrial myocardium. It provokes natri-
uresis and diuresis via the GCase-cGMP axis. It may lower sodium reabsorption by
antagonizing action of angiotensin-2 in the proximal tubule. It is a potent vasoactive
agent. It has a greater resistance to degradation by neutral endopeptidase than other
natriuretic peptides.

∼

5.6.2 Hemojuvelin-Hepcidin Regulation

Hemojuvelin is mainly expressed in skeletal and cardiac muscles and, to a lesser
extent, the liver. It modulates the expression of the HAMP gene that encodes
hepcidin, via the bone morphogenetic protein pathway [ 406 , 407 ]. Hepcidin is
a liver-derived iron-regulatory peptide acting on cells to limit iron flux toward
the plasma. Hepcidin deficiency induces iron overload, whereas hepcidin excess
induces anemia.

5.7 Energy Supply and Reserve

Energy provider ATP is required for both cell viability and myocardial pump
activity. Most ATP is synthesized by substrate oxidation in mitochondria that have
a high density in cardiomyocytes. Mitochondria-derived ATP is mainly used for
cardiac contraction, whereas ATP produced by glycolysis intervenes in activity of
kinases and ion pumps and channels (e.g., Ca 2 + -calmodulin-dependent kinase-2,
ATP-sensitive K + channels, Na + -K + AT P a s e , a n d C a 2 + ATPase SERCA2).
At rest, fatty acid oxidation covers more than 70% of energy need. The remainder
comes from oxidation of carbohydrates, principally glucose. Although oxidation of
glucose is more efficient than that of fatty acid, fatty acid oxidation provides much
more ATP than glucose. In healthy heart, selection among lipids and carbohydrates
is governed by plasma substrate availability and hormonal regulation (insulin,
catecholamines). When heart activity raises, additional sources of ATP synthesis,
such as glycogenolysis, glycolysis, and phosphotransferase reactions catalyzed by
creatine kinase and adenylate kinase, are involved (Fig. 5.11 ).