Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 298

filaments and microtubules that can be used for selective molecular transfer. They
indeed allow mitochondria exchange and calcium signal propagation between the
2 cell types.

6.2.1.2 Myofibroblast-Myocyte Coupling

Cardiofibroblasts contribute to the regulation of the myocardial function as well as
myocardial remodeling in maladaptive hypertrophy of cardiomyocytes during hy-
pertension and after myocardial infarction, among other heart diseases. Myocardial
remodeling results from fibroblast proliferation and increased collagen synthesis.
In response to injury, fibroblasts proliferate and differentiate into myofibroblasts .
The latter secrete collagen and synthesize smooth muscle α -actin, stretch-sensitive

ion channels, and connexins.
Myofibroblasts can interrupt normal between-myocyte coupling; cardiac
fibrosis promotes arrhythmias. Moreover, myofibroblasts can form gap junctions
with myocytes, at least in cocultures. The lower negative resting potential of
fibroblast plasma membrane can then contribute to depolarization of myocytes.
Myofibroblast-myocyte gap junction current comprise an early, transient outward
( i K , to )-like component and a late, sustained component. Coupling of myocytes to
myofibroblasts promotes early afterdepolarizations due to the former, especially
when myocyte repolarization reserve iss reduced by oxidative or ionic stress [ 570 ].

6.2.1.3 Effects of Natriuretic Peptides

Numerous growth factors and vasoactive peptides, such as transforming growth
factor- , angiotensin-2, and endothelin-1, participate in maladaptive cardiomyocyte

hypertrophy, fibroblast proliferation, and augmented interstitial deposition. Con-
versely, antagonists of myocyte hypertrophy and fibrosis exist, such as type-A, -B,
and -C natriuretic peptides.
Natriuretic peptides, such as ANP and BNP, are released from cardiomyocytes.
They then act as auto-, juxta-, and paracrine factors to reduce cardiomyocyte
maladaptive hypertrophy and exert antifibrotic and antiproliferative effects on
cardiofibroblasts.
Brain natriuretic peptide limits the production of collagen-1 and fibronectin,
myofibroblast conversion estimated by

β

-smooth muscle actin, fibroblast pro-
liferation assessed by PDGFa and IGF1, and inflammation evaluated by COx2
and IL6 levels. C-type natriuretic peptide released from endothelial cells and
cardiofibroblasts also has antifibrotic effects.
Cardiofibroblasts synthesize guanylate cyclase receptors NP 1 and NP 2 (NPRa
and NPRb, or GC2a and GC2b) as well as the natriuretic peptide clearance receptor
NP 3 (NPRc; Vol. 3 - Chap. 6. Receptors).

α