Maresin-1 appears to exhibit protective effects against pulmonary arterial hypertension (PAH) and may represent a potential target for PAH prevention and treatment, according to a study published in the Journal of Molecular and Cellular Cardiology.
To examine the role of maresin-1 in the development and progression of PAH, the researchers analyzed the effect of maresin-1 treatment on PAH in both monocrotaline-induced rat and hypoxia+SU5416-induced mouse models of pulmonary hypertension.
They collected plasma samples from rodent pulmonary hypertension models as well as patients with PAH to examine maresin-1 production. The function of maresin-1 receptors was blocked by adding specific shRNA adenovirus or inhibitors.
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According to the results, maresin-1 exhibited protective effects against the development and progression of pulmonary hypertension in rodents. However, the blockage of maresin-1 receptor lipoxin A4 with BOC-2 eliminated the positive effects of maresin-1 treatment against PAH development and reduced its therapeutic potential. The blockage of other maresin-1 receptors such as LGR6 or RORα caused no such results.
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Moreover, the researchers demonstrated that the maresin-1/lipoxin A4 receptor axis suppressed hypoxia-induced pulmonary arterial smooth muscle cell proliferation and reduced the intensity of pulmonary vascular remodeling by inhibiting mitochondrial accumulation of heat shock protein 90α and restoring mitophagy.
“Although the current therapeutic drugs significantly improved symptoms, they are limited in reversing pulmonary vascular remodeling and decreasing mortality. For most patients, PAH is still a life-limiting disease, with no prospect of cure,” Liu and colleagues explained.
“These observations broaden our in-depth understanding of the role of maresin-1 in PAH. Targeting maresin-1/lipoxin A4 receptor/heat shock protein 90α signaling may be used therapeutically in PAH treatment.”
PAH is marked by intense proliferation of pulmonary arterial smooth muscle cells as well as increased pulmonary vascular remodeling. Maresin-1 is one of the pro-resolving lipid mediators that is known to exhibit protective effects on several inflammation-related diseases.
References
Liu M, He H, Fan F, et al. Maresin-1 protects against pulmonary arterial hypertension by improving mitochondrial homeostasis through ALXR/HSP90α axis. J Mol Cell Cardiol. Published online May 25, 2023. doi:10.1016/j.yjmcc.2023.05.005
