Niacin Attenuates Pulmonary Hypertension Through H-PGDS in Macrophages
| Autor: | Ankang Lyu, Yuhu He, Michael Lazarus, Jiao Liu, Peiyuan Bai, Jian Zhang, Han Chen, Yunchao Su, Qian Zhu, Ying Yu, Daile Jia, Guilin Chen, Naifu Wan, Chen Wang, Jing Wang, Yujun Shen, Yoshihiro Urade |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Physiology Hypertension Pulmonary Pulmonary Artery Niacin chemistry.chemical_compound Mice Internal medicine medicine Macrophage Perivascular inflammation Animals Humans Lung Antihypertensive Agents Cells Cultured Hypolipidemic Agents business.industry Prostaglandin D2 Macrophages medicine.disease Pulmonary hypertension Rats Intramolecular Oxidoreductases Endocrinology Hematopoietic prostaglandin D synthase chemistry Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation research. 127(10) |
| ISSN: | 1524-4571 |
| Popis: | Rationale: 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. |
| Databáze: | OpenAIRE |
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