Pulmonary hypertension (PH) is a debilitating and eventually fatal disease that is resistant to current therapeutics. A defining characteristic of pulmonary hypertension (PH) is the extensive remodeling of pulmonary arteries (PAs), which results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. The identification of novel molecular mechanisms that underlie increased proliferation, reduced apoptosis, and excessive extracellular matrix production in pulmonary artery smooth muscle cells (PASMCs) is vital. The recent papers published in the Am J Respir Crit Care Med and Am J Physiol Lung Cell Mol Physiol journals found the importance of increased Gal-3 expression and signaling on PA vascular remodeling and cardiopulmonary function in experimental models of PH. In rat models of PH, they observed increased Gal-3 expression in PASMCs, which stimulated migration and resistance to apoptosis, whereas silencing or genetic deletion reduced cellular migration and PA fibrosis and increased apoptosis. Gal-3 inhibitors attenuated and reversed PA remodeling and fibrosis, as well as hemodynamic indices in monocrotaline (MCT)-treated rats in vivo. The elevated Gal-3 levels contribute to inappropriate PA remodeling in PH by enhancing multiple profibrotic mechanisms. Therapeutic strategies targeting Gal-3 may be of benefit in the treatment of PH.
1. Barman, Scott A(*); Chen, Feng(*); Li, Xueyi; Haigh, Stephen; Stepp, David W; Kondrikov, Dmitry; Mahboubi, Keyvan; Bordan, Zsuzsanna; Traber, Peter; Su, Yunchao; Fulton, David J R(*), Galectin-3 Promotes Vascular Remodeling and Contributes to Pulmonary Hypertension., Am J Respir Crit Care Med. 2018 Jun 1;197(11):1488-1492.
2. Barman Scott A(*); Li Xueyi; Haigh Stephen; Kondrikov Dmitry; Mahboubi Keyvan; Bordan Zsuzsanna; Stepp David W; Zhou Jiliang; Wang Yusi; Weintraub Daniel S; Traber Peter; Snider William; Jonigk Danny; Sullivan Jennifer C; Crisli
