Pulmonary vascular disease & thromboembolism
Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension
Authors' conclusion
Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions.
Study context
- Population
- Mouse models of hypoxia- and SU5416/hypoxia (SuHx)-induced pulmonary hypertension (PH); lung tissue of patients with PH; pulmonary artery endothelial cells
- Comparison
- ME1 inactivation vs intact ME1
Methodological detailsglobal and endothelial-specific ME1 knockout mice, hypoxia- and SuHx-induced PH models
- Global and endothelial-specific ME1 knockout mice
- Hypoxia- and SuHx-induced PH models
Main finding
As reported in the abstract
- ME1 protein level and enzymatic activity highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells
- Global ME1 knockout protected mice from hypoxia- or SuHx-induced PH
- Endothelial-specific ME1 deletion attenuated pulmonary vascular remodeling and PH development
- ME1 inhibition promoted adenosine production and A2AR-mediated signaling, increasing nitric oxide and decreasing proinflammatory molecule expression in endothelial cells
- Pharmacological ME1 inactivation attenuated PH progression in preventive and therapeutic settings
Original publication
Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension. Circulation. Published 5 February 2024. doi:10.
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