In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. 10 ( 2020-10-23), p. 1323-1336
Abstract:
Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling, accompanied by varying degrees of perivascular inflammation. Niacin, a commonly used lipid-lowering drug, possesses vasodilating and proresolution effects by promoting the release of prostaglandin D 2 (PGD 2 ). However, whether or not niacin confers protection against PAH pathogenesis is still unknown. Objective: This study aimed to determine whether or not niacin attenuates the development of PAH and, if so, to elucidate the molecular mechanisms underlying its effects. Methods and Results: Vascular endothelial growth factor receptor inhibitor SU5416 and hypoxic exposure were used to induce pulmonary hypertension (PH) in rodents. We found that niacin attenuated the development of this hypoxia/SU5416–induced PH in mice and suppressed progression of monocrotaline-induced and hypoxia/SU5416–induced PH in rats through the reduction of pulmonary artery remodeling. Niacin boosted PGD 2 generation in lung tissue, mainly through H-PGDS (hematopoietic PGD 2 synthases). Deletion of H-PGDS, but not lipocalin-type PGDS, exacerbated the hypoxia/SU5416–induced PH in mice and abolished the protective effects of niacin against PAH. Moreover, H-PGDS was expressed dominantly in infiltrated macrophages in lungs of PH mice and patients with idiopathic PAH. Macrophage-specific deletion of H-PGDS markedly decreased PGD 2 generation in lungs, aggravated hypoxia/SU5416–induced PH in mice, and attenuated the therapeutic effect of niacin on PAH. Conclusions: Niacin treatment ameliorates the progression of PAH through the suppression of vascular remodeling by stimulating H-PGDS–derived PGD 2 release from macrophages.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.120.316784
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
detail.hit.zdb_id:
1467838-X
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