316
[ 27 ], which may have contributed to improve cardiac capillary density in MCT-
induced PAH [ 32 , 33 ].
Oxidative stress has been implicated in RV maladaptive remodeling and dysfunc-tion [ 57 , 74 ]. By decreasing hydrogen peroxide production (H 2 O 2 ), ExT training
modulated the apoptosis regulator BAX/B-cell lymphoma 2 (Bax/Bcl-2) and cas-
pase-3, thus decreasing apoptotic signaling in RV myocardium of MCT rats [ 26 ]. As
major sources of reactive oxygen and nitrogen species (RONS), mitochondria them-
RV (^) LV
RV LV^
PAH without ExTPAHwithExT
RV (^) LV
ÝVascularization
Extracellularmatrix
ßFibrosis
ßMMP-9andÝMMP-2
Contractileproteins
ßBeta/alpha-MHC
Inflammation
ßleucocyteinfiltration^4
ßTNF-alpha/IL-10ratio
ßTWEAK
ÝNF-kB p105/p50 and p65
Neurohumoral
ÝVEGF
ÝApelin
ßBNP
ßET-1
Celldeath
ßBax/BcL 2
ßcaspase-3
RONS
ß H 2 O 2
ß3-nitrotyrosine
Metabolism
ß GLUT1
ÝMitochondrialcomplex V activity
Hypertrophy/Proteindegradation
ÝpAkt
ßAtrogin
ßp-GSK-3/GSK-3
ßVascularization
Extracellularmatrix
ÝFibrosis
ÝMMP-9andÛMMP-2
Contractileproteins
ÝBeta/alpha-MHC
Inflammation
Ýleucocyteinfiltration
ÝTNF-alpha/IL-10ratio
ÛTWEAK
ÛNf-kB p105/p50 and p65
Neurohumoral
ßVEGF
ßApelin
ÝBNP
ÝET-1
Celldeath
ÝBax/BcL2
Ýcaspase- 3
RONS
ÝH 2 O 2
Ý3-nitrotyrosine
Metabolism
ÝGLUT1
ßMitochondrialcomplex V activity
Hypertrophy/Proteindegradation
ßpAkt
ÝAtrogin
Ýp-GSK-3/GSK-3
CardiacFunction
ßsystolic function
ßdiastolic function
CardiacStructure
Ýhypertrophy
Ý dilation
CardiacFunction^1
Ýsystolic function
Ýdiastolic function
CardiacStructure
ÝHypertrophy^2
ß dilation^3
Healthy
Legend:
1
ExT seems to worsen RV function in severe decompensated PAH.
2
ExT seems to worsen RV dilation in severe decompensated PAH.
(^3) ExT was shown to decrease RV mass in a few studies, which is probably
related to a decrease in pulmonary resistance and pulmonary artery
hypertrophy. In the majority of the studies, RV hypertrophy remained
increased after ExT.
(^4) ExT induced an increase in RV leucocyte infiltration only in severe
decompensated PAH.
Fig. 17.2 Summary of the main changes induced by Exercise Training in the Right Ventricle of
animals with Pulmonary Arterial Hypertension
(^1) ExT seems to worsen RV function in severe decompensated PAH
(^2) ExT seems to worsen RV dilation in severe decompensated PAH
(^3) ExT was shown to decrease RV mass in a few studies, which is probably related to a decrease in
pulmonary resistance and pulmonary artery hypertrophy. In the majority of the studies, RV hyper-
trophy remained increased after ExT
(^4) ExT induced an increase in RV leucocyte infiltration only in severe decompensated PAH
D. Moreira-Gonçalves et al.