Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 249

5.8.2.9 AKAPs

Several AKAPs are detected in cardiomyocytes, such as AKAP1, AKAP5,

AKAP7 , and AKAP8 to AKAP13, and related proteins that act as AKAPs,

such as ezrin, BIG2, sphingosine kinase type-1-interacting protein (SKIP),
and the intermediate filament protein that localizes to Z lines, desmuslin (or
synemin) [ 420 , 421 ].
A-kinase anchoring protein-13 is a Rho-specific guanine nucleotide-exchange
factor (RhoGEF13). It activates RhoA involved in certain pathways of cardiomy-
ocyte hypertrophy, transducing hypertrophic signals from

α

α 1-adrenergic receptors

coupled to G 12 [ 422 ]. Inactivation occurs via AKAP13 phosphorylation by

anchored PKA and subsequent recruitment of 14-3-3 regulator.

α

5.8.2.10 Prostaglandins

Prostaglandin-E2 acts via its EP 4 receptor coupled to the Gs-AC-cAMP-PKA
axis. It causes hypertrophy of neonatal ventricular myocytes via ERK1 and ERK2
kinases. The EP 4 -PKA pathway stimulates Rap GTPase that activates ERK1 and
ERK2 and then 90-kDa ribosomal S6 kinase (RSK) [ 423 ]. The EP 4 -PKA-ERK1/2-
RSK cascade stimulates Fos and synthesis of B-type natriuretic peptide. In addition,
ERK1, ERK2, and RSK also contribute to PGE2 regulation of the transcription
factor early growth response-1 (EGR1).

5.8.2.11 Epoxyeicosatrienoic Acids

Epoxyeicosatrienoic acids impede NF B activation, thus having beneficial effects

on cardiac hypertrophy. Soluble epoxide hydrolase (sEH) catalyzes the conver-
sion of cardioprotective epoxyeicosatrienoic acids, mainly (14,15)EETs that act
via STAT3 factor [ 424 ], into dihydroxyeicosatrienoic acids. Inhibitors of soluble
epoxide hydrolase that indirectly block NF

κ

B activation, preserve cardiomyocytes
and can prevent development of cardiac hypertrophy as well as cardiac arrhythmias
associated with cardiac hypertrophy in murine model with aortic banding [ 425 ].

κ

5.8.2.12 Cardiotrophin

Cardiotrophin-1, a member of the IL6 cytokine family and one of the most potent
cardiac myocyte survival factors, acts via GP130 cytokine receptor. Cardiotrophin-1
stimulates the JaK2-STAT3 pathway and induces cardiac myocyte hypertrophy.
Cardiotrophin-1 phosphorylates STAT3 factor. Activated STAT3 increases
angiotensinogen expression in cardiomyocytes (autocrine regulation) [ 426 ].
Cardiotrophin-1 binds to IL6R-GP130 dimer and triggers the signaling cascade
that also involves MAPK enzymes.