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Videomorphometric Analysis of Hypoxic Pulmonary Vasoconstriction of Intra-pulmonary Arteries Using Murine Precision Cut Lung Slices
Published on: January 14, 2014
Parathyroid Hormone Contributes to Pulmonary Hypertension in Hypoxic Conditions.
Yusuke Joki1,2, Hakuoh Konishi1,3, Kiyoshi Takasu4
1Department of Cardiovascular Biology and Medicine (Y.J., H.K., G.K., Y.Y., T.F., T.M.), Juntendo University Graduate School of Medicine, Tokyo, Japan.
High parathyroid hormone (PTH) levels are linked to pulmonary hypertension (PH). Targeting the PTH receptor (PTH1R) may offer a new therapeutic strategy for PH.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pulmonary Medicine
Background:
- Pulmonary hypertension (PH) is a severe condition characterized by elevated pulmonary artery pressure, potentially leading to right heart failure.
- Parathyroid hormone (PTH) is vital for calcium homeostasis and influences cardiovascular health.
- This study investigated the potential role of PTH in the pathogenesis of PH.
Purpose of the Study:
- To determine the association between serum PTH levels and PH in patients.
- To investigate the effect of PTH and its receptor (PTH1R) on PH development in animal models.
- To explore the cellular mechanisms underlying PTH's action on pulmonary artery smooth muscle cells.
Main Methods:
- Serum PTH levels were measured in patients undergoing right heart catheterization for PH evaluation.
- PH was induced in mouse and rat models to study the effects of PTH regulation and PTH1R.
- Human pulmonary artery smooth muscle cells were used for in vitro studies on PTH1R regulation and PTH effects.
Main Results:
- Serum PTH concentration correlated with pulmonary artery pressure and resistance, with a specific cutoff value predicting PH.
- In animal models, PTH exacerbated right ventricular hypertrophy, while PTH reduction attenuated it.
- PTH promoted pulmonary artery smooth muscle cell proliferation and migration via the PTH1R-β-arrestin-ERK pathway.
Conclusions:
- PTH/PTH1R signaling is implicated in the development and progression of PH.
- PTH1R represents a potential therapeutic target for PH.
- Further research into PTH/PTH1R signaling is warranted for PH treatment strategies.
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