Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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and possibly cellular trans-differentiation (i.e., endothelial- mesenchymal transfor-

mation) [ 83 ]. In addition, severe forms of PAH often present with vaso- occlusive

lesions, involving PASMCs, endothelial cells and possibly cells of non- vascular

origin. The greatest influence on PVR comes from changes in small arterioles; how-

ever, decreased compliance (i.e., increased stiffness) in the elastic proximal pulmo-

nary arteries may also contribute for RV afterload [ 83 ].

Current knowledge about the impact of ExT on pulmonary architecture and/or

vascular function is far more limited than for RV. From the 16 studies addressing ExT

in PAH, only 6 reported measurements of pulmonary artery thickness (Table 17.2).

The hypertrophy of the arteries was found to be reduced [ 25 , 29 , 84 ], to suffer no

significant changes [ 27 , 30 , 33 ], or to be aggravated [ 33 ] after ExT. The worst outcome

occurred when ExT was performed in the setting of advanced disease [ 33 ]. Regarding

PAH without ExT

Structuralchanges

ÝßÛpulmonary artery wallthickness

ßpulmonary vesselmuscularization

Functionalchanges

ßÛpulmonary vascular resistance

Molecularchanges

ÝNO-mediatedpulmonary vasodilatation

Ûresponsiveness tovasoconstrictors

Ûresponsiveness tovasodilators

ÝH 2 O 2 /VEGF/p-Akt

PAH with ExT

Structuralchanges

Ýpulmonary artery wallthickness

Ýpulmonary vesselmuscularization

Functionalchanges

Ýpulmonary vascular resistance

Molecularchanges

ßNO-mediatedpulmonary vasodilatation

Ýresponsiveness tovasoconstrictors

ßresponsiveness tovasodilators

ßH 2 O 2 /VEGF/p-Akt

Healthy

Fig. 17.3 Summary of the main changes induced by Exercise Training in the lungs of animals
with Pulmonary Arterial Hypertension (Note: The impact of ExT on pulmonary artery wall thick-
ness is inconclusive. Arrows in the blue box denote the direction of changes in comparison to
sedentary healthy animals. Arrows in the green box denote the direction of changes in comparison
to sedentary animals with PAH)

D. Moreira-Gonçalves et al.