TY - JOUR
T1 - Galectin-3
T2 - A Harbinger of Reactive Oxygen Species, Fibrosis, and Inflammation in Pulmonary Arterial Hypertension
AU - Fulton, David J.R.
AU - Li, Xueyi
AU - Bordan, Zsuzsanna
AU - Wang, Yusi
AU - Mahboubi, Keyvan
AU - Rudic, R. Daniel
AU - Haigh, Stephen
AU - Chen, Feng
AU - Barman, Scott A.
N1 - Publisher Copyright:
© 2019, Mary Ann Liebert, Inc., publishers.
PY - 2019/11/10
Y1 - 2019/11/10
N2 - Significance: Pulmonary arterial hypertension (PAH) is a progressive disease arising from the narrowing of pulmonary arteries (PAs) resulting in high pulmonary arterial blood pressure and ultimately right ventricle (RV) failure. A defining characteristic of PAH is the excessive and unrelenting inward remodeling of PAs that includes increased proliferation, inflammation, and fibrosis. Critical Issues: There is no cure for PAH nor interventions that effectively arrest or reverse PA remodeling, and intensive research over the past several decades has sought to identify novel molecular mechanisms of therapeutic value. Recent Advances: Galectin-3 (Gal-3) is a carbohydrate-binding lectin remarkable for its chimeric structure, composed of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 has been identified as a regulator of numerous changes in cell behavior that contributes to aberrant PA remodeling, including cell proliferation, inflammation, and fibrosis, but its role in PAH has remained poorly understood until recently. In contrast, pathological roles for Gal-3 have been proposed in cancer and inflammatory and fibroproliferative disorders, such as pulmonary vascular and cardiac fibrosis. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH. We provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species production, NADPH oxidase enzyme expression, and redox signaling, which have been shown to contribute to both vascular remodeling and increased pulmonary arterial pressure. Future Directions: While several preclinical studies suggest that Gal-3 promotes hypertensive pulmonary vascular remodeling, the clinical significance of Gal-3 in human PAH remains to be established. Antioxid. Redox Signal. 00, 000-000.
AB - Significance: Pulmonary arterial hypertension (PAH) is a progressive disease arising from the narrowing of pulmonary arteries (PAs) resulting in high pulmonary arterial blood pressure and ultimately right ventricle (RV) failure. A defining characteristic of PAH is the excessive and unrelenting inward remodeling of PAs that includes increased proliferation, inflammation, and fibrosis. Critical Issues: There is no cure for PAH nor interventions that effectively arrest or reverse PA remodeling, and intensive research over the past several decades has sought to identify novel molecular mechanisms of therapeutic value. Recent Advances: Galectin-3 (Gal-3) is a carbohydrate-binding lectin remarkable for its chimeric structure, composed of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 has been identified as a regulator of numerous changes in cell behavior that contributes to aberrant PA remodeling, including cell proliferation, inflammation, and fibrosis, but its role in PAH has remained poorly understood until recently. In contrast, pathological roles for Gal-3 have been proposed in cancer and inflammatory and fibroproliferative disorders, such as pulmonary vascular and cardiac fibrosis. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH. We provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species production, NADPH oxidase enzyme expression, and redox signaling, which have been shown to contribute to both vascular remodeling and increased pulmonary arterial pressure. Future Directions: While several preclinical studies suggest that Gal-3 promotes hypertensive pulmonary vascular remodeling, the clinical significance of Gal-3 in human PAH remains to be established. Antioxid. Redox Signal. 00, 000-000.
KW - PAH
KW - fibrosis
KW - galectin-3
KW - inflammation
KW - pulmonary hypertension
KW - reactive oxygen species
KW - vascular remodeling
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U2 - 10.1089/ars.2019.7753
DO - 10.1089/ars.2019.7753
M3 - Review article
C2 - 30767565
AN - SCOPUS:85066463388
SN - 1523-0864
VL - 31
SP - 1053
EP - 1069
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 14
ER -