Exercise Benefits in Pulmonary Hypertension

• Published in: Journal of the American College of Cardiology Vol. 73; no. 22; pp. 2906 - 2907
• Main Authors: Santos-Lozano, Alejandro, Fiuza-Luces, Carmen, Fernández-Moreno, David, Llavero, Francisco, Arenas, Joaquín, López, Juan Antonio, Vázquez, Jesús, Escribano-Subías, Pilar, Zugaza, José L., Lucia, Alejandro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.06.2019; Elsevier Limited
• Subjects: Aged; Angiopoietin; Anticoagulants; Artificial intelligence; Biology; Cardiology; Cardiovascular; Cell adhesion & migration; Cell adhesion molecules; Combined Modality Therapy; Connective tissue diseases; Elastase; Endothelins; Etiology; Exercise; Extracellular matrix; Female; Fibroblast growth factor 2; Fibronectin; Fitness training programs; Growth factors; Humans; Hypertension; Hypertension, Pulmonary - physiopathology; Hypertension, Pulmonary - rehabilitation; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; Intestine; Kinases; Male; MAP kinase; Mesenchyme; Middle Aged; Neural cell adhesion molecule; Neural networks; Neuropilin; Neuropilin-1 - physiology; Osteonectin; Phosphodiesterase; Physical Fitness - physiology; Proteins; Proteome - physiology; Transforming growth factor-b; Vascular Remodeling - physiology; Vasoactive agents; Vasoconstriction
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2019.03.489

To minimize the risk of bias given the multifactorial etiology of PAH, resting samples for proteomic analyses were collected before and after the RCT only in those participants (n = 9 [5 from intervention group, 1 male, age 35 to 53 years] and 4 control subjects [1 male; age 40 to 56 years]) presenting with homogeneous pathophysiology (idiopathic, hereditary, or connective tissue disease-associated PAH) and treatment (oral anticoagulants + phosphodiesterase-5 inhibitors + endothelin-receptor antagonists). Wilcoxon’s test, to identify proteins that were differentially expressed as a result of the 8-week exercise training intervention (vs. the control group); and threshold-based cross-validation methods, to identify proteins with the best between-group classifier potential (with “good classifiers” allowing assignment of a given plasma sample to 1 of the 2 patient groups, exercise or control [p value of accuracy cross-validation <0.05, applying leave-one-out analysis]). Control (Wilcoxon-Test p Value) Interactions With PAH Effectors (Identified by Gene Name) Artificial Neural Network Scores (0–100) for the Corresponding Effector Motif Main Process (Effector Motif) in Which the Candidate Protein Is Involved Cathepsin-D ⨯ 0.357 ✓ 0.032 (↓) ✓ Elastase, neutrophil expressed (ELANE), fibronectin-1 (FN1), mitogen-activated protein kinase (MAPK)1 ✓ (PAH, 59; pulmonary vascular remodeling, 50) Pulmonary vascular remodeling Neural cell adhesion molecule 1 (NCAM1) ✓ 0.040 ✓ 0.016 (↓) ✓ Angiopoietin- 1, epidermal growth receptor factor (EGRF), fibroblast growth factor 2 (FGF2), platelet-derived growth factor (PDGF) subunit A (PDGFA) and B (PDGFB), and receptor A (PDGFRA) and B (PDGFRB), tyrosine kinase endothelial (TEK) ✓ (PAH, 72; pulmonary vascular remodeling, 64; pulmonary vasoconstriction, 70) Pulmonary vascular remodeling Neuropilin-1 ✓ 0.048 ⨯ 0.190 ✓ FGF2, integrin α-5 (ITGA5), PDGFB, transforming growth factor β receptor 1 (TGFBR1), tumor necrosis (TNF)α ✓ (PAH, 71; pulmonary vascular remodeling, 46; endothelial-to-mesenchymal transition, 65) Pulmonary vascular remodeling Profilin-1 ✓ 0.405 ✓ 0.032 (↓) ✓ FN1, hypoxia-inducible factor 1-alpha (HIF1A), MAPK3, vasoactive intestinal polypeptide receptor 1 (VIPR1) ✓ (PAH, 69; pulmonary vasoconstriction, 67) Pulmonary vasoconstriction SPARC-like protein 1 (SPARCL1) ⨯ 0.405 ✓ 0.032 (↑) ✓ EGRF, TNFα ✓ (PAH, 72; pulmonary inflammation, 60) Pulmonary vascular remodeling, vascular extracellular matrix remodeling Table 1 Candidate Proteins Linked to Exercise Training Benefits in PAH