The role of apelin in the pulmonary circulation

Brash, Lauren (2017) The role of apelin in the pulmonary circulation. MD thesis, University of Glasgow.

Abstract

Background – Apelin agonism causes vasodilatation and increased cardiac contractility in humans and improves pulmonary arterial hypertension in animal models. We here aimed to determine the pulmonary haemodynamic effects of apelin in patients with pulmonary arterial hypertension (PAH) and to determine the effects of apelin on rat pulmonary artery fibroblasts in the lab.

Methods and Results – In a double-blind randomized crossover study, 19 patients with PAH received intravenous (Pyr1)apelin-13 (10-100 nmol/min) and matched saline placebo during invasive right heart catheterization and measurement of pulmonary artery pressure, pulmonary artery wedge pressure, cardiac output. Acute (Pyr1)apelin-13 infusion caused a reduction in pulmonary vascular resistance (p=0.001), increased cardiac output (p<0.0001) and an increase in stroke volume (p<0.0001).
Apelin also prevented the hypoxic hyperproliferation and migration of rat pulmonary artery fibroblasts and reduced the activity of p38 MAP kinase.

Conclusions – Acute intravenous (Pyr1)apelin infusion reduces pulmonary vascular resistance and increases cardiac output and stroke volume in patients with PAH. It also prevented fibroblast proliferation and migration and reduced the activity of the p38 MAP kinase pathway. Apelin agonism is an novel potential therapeutic target for the treatment of PAH and appears to improve both the haemodynamic consequences of pulmonary hypertension as well as potentially improving the remodelling seen in the pulmonary vasculature of patients with pulmonary hypertension.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Keywords: Apeli, pulmonary hypertension, clinical trial.
• Subjects: Q Science > Q Science (General); R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Funder's Name: British Heart Foundation (BHF)
• Supervisor's Name: Peacock, Professor Andrew and Welsh, Dr. David
• Date of Award: 2017
• Depositing User: Dr Lauren Brash
• Unique ID: glathesis:2017-8128
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Apr 2017 08:05
• Last Modified: 04 Apr 2019 13:13
• URI: https://theses.gla.ac.uk/id/eprint/8128