Abstract
Endothelial dysfunction is a hallmark of pulmonary arterial hypertension (PAH) but there are no established methods to study pulmonary artery endothelial cells (PAECs) from living patients. We sought to culture PAECs from pulmonary artery catheter (PAC) balloons used during right-heart catheterisation (RHC) to characterise successful culture attempts and to describe PAEC behaviour.
PAECs were grown in primary culture to confluence and endothelial cell phenotype was confirmed. Standard assays for apoptosis, migration and tube formation were performed between passages three to eight. We collected 49 PAC tips from 45 subjects with successful PAEC culture from 19 balloons (39%).
There were no differences in subject demographic details or RHC procedural details in successful versus unsuccessful attempts. However, for subjects who met haemodynamic criteria for PAH, there was a higher but nonsignificant (p=0.10) proportion amongst successful attempts (10 out of 19, 53%) versus unsuccessful attempts (nine out of 30, 30%). A successful culture was more likely in subjects with a lower cardiac index (p=0.03) and higher pulmonary vascular resistance (p=0.04). PAECs from a subject with idiopathic PAH were apoptosis resistant compared to commercial PAECs (p=0.04) and had reduced migration compared to PAECs from a subject with portopulmonary hypertension with high cardiac output (p=0.01). PAECs from a subject with HIV-associated PAH formed fewer (p=0.01) and shorter (p=0.02) vessel networks compared to commercial PAECs.
Sustained culture and characterisation of PAECs from RHC balloons is feasible, especially in PAH with high haemodynamic burden. This technique may provide insight into endothelial dysfunction during PAH pathogenesis.
Abstract
Pulmonary artery endothelial cells (PAECs) from pulmonary artery catheter balloons used during routine right heart catheterisation can be cultured and sustained to study endothelial cell dysfunction at various stages of pulmonary hypertension http://bit.ly/2RL6dTc
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00122-2020
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: C.E. Ventetuolo reports grants from National Institutes of Health (R01 HL141268 and P20GM103652), during the conduct of the study; institutional grants from United Therapeutics and Eiger; personal fees from Acceleron Pharma, outside the submitted work; and her spouse was a recent employee of CVS Health.
Conflict of interest: J.M. Aliotta has nothing to disclose.
Conflict of interest: J. Braza has nothing to disclose.
Conflict of interest: H. Chichger has nothing to disclose.
Conflict of interest: M. Dooner has nothing to disclose.
Conflict of interest: D. McGuirl has nothing to disclose.
Conflict of interest: C.J. Mullin has nothing to disclose.
Conflict of interest: J. Newton has nothing to disclose.
Conflict of interest: M. Pereira has nothing to disclose.
Conflict of interest: A. Princiotto has nothing to disclose.
Conflict of interest: P.J. Quesenberry has nothing to disclose.
Conflict of interest: T. Walsh has nothing to disclose.
Conflict of interest: M. Whittenhall has nothing to disclose.
Conflict of interest: J.R. Klinger has nothing to disclose.
Conflict of interest: E.O. Harrington has nothing to disclose.
Support statement: This work was completed with support from an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (P20 GM103652) and a National Institutes of Health grant (R01-HL141268). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received July 3, 2019.
- Accepted December 10, 2019.
- Copyright ©ERS 2020