Cardiac and Immune Functional Proteins are altered during CCS
The results obtained from mRNAs and protein levels demonstrates
alteration in the expressions of βARs, ACs, GRK2 and GRK5 in the
myocardium during CCS compared with under normal physiological
conditions (Supplementary Fig. S2a and S2b). Specifically, βARs, AC5,
and AC7 were found depleting while AC6, GRK2 and GRK5 were upregulated
in the PCH mice hearts.
Overexpression of GRK5 in the hearts of PCH mice must have facilitated
its translocation and localization to the nucleus of cardiomyocytes to
mediate the exacerbation of PCH as evident by both atrial natriuretic
peptide (ANP) and brain natriuretic peptide (BNP) upregulations
(Supplementary Fig. S2a and S2b) (Hullmann JE et al., 2014).
cAMP concentrations assessed by ELISA to ascertain the impact of AC5,
AC6 and AC7 alterations showed no significant differences between Ctrl
and Vhl mice. However, cAMP concentration in PCH mice was significantly
decreased compared with both Vhl and Ctrl mice (Supplementary Fig. S2c).
Also, extracellular signal-regulated kinase (ERK1/2) and cardiac
hypertrophy and inflammatory TFs; GATA4, nuclear factor of activated T
cells (NFAT), myocyte enhancer factor-2 (MEF2) and nuclear factor
kappa-light-chain-enhancer of activated B cells (NF-κB) were all
comparably fairly expressed in the hearts of Ctrl and Vhl mice but
overexpressed in PCH mice hearts (Supplementary Fig. S3).