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Circulating microparticles in severe pulmonary arterial hypertension increase intercellular adhesion molecule-1
Leslie A Blair1,2, April K Haven1,2, Natalie N Bauer3,4
1Department of Pharmacology, College of Medicine, University of South Alabama, 5851 USA Drive North, MSB 3340, Mobile, AL, 36688, USA.
Background:
Microparticles (MPs) stimulate inflammatory adhesion molecule expression in systemic vascular diseases, however it is unknown whether circulating MPs stimulate localized ICAM-1 expression in the heterogeneically distinct pulmonary endothelium during pulmonary arterial hypertension (PAH). Pulmonary vascular lesions with infiltrating inflammatory cells in PAH form in the pulmonary arteries and arterioles, but not the microcirculation. Therefore, we sought to determine whether circulating MPs from PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression.
Results:
Pulmonary artery endothelial cells (PAECs) were exposed to MPs isolated from the circulation of a rat model of severe PAH. During late-stage (8-weeks) PAH, but not early-stage (3-weeks), an increase in ICAM-1 was observed. To determine whether PAH MP-induced ICAM-1 was selective for a specific segment of the pulmonary circulation, pulmonary microvascular endothelial cells (PMVECs) were exposed to late-stage PAH MPs and no increase in ICAM-1 was detected. A select population of circulating MPs, the late-stage endoglin + MPs, were used to assess their ability to stimulate ICAM-1 and it was determined that the endoglin + MPs were sufficient to promote ICAM-1 increases in the whole cell, but not surface only expression.
Conclusions:
Late-stage, but not early-stage, MPs in a model of severe PAH selectively induce ICAM-1 in pulmonary artery endothelium, but not pulmonary microcirculation. Further, the selected endoglin + PAH MPs, but not endoglin + MPs from control, are sufficient to promote whole cell ICAM-1 in PAECs. The implications of this work are that MPs in late-stage PAH are capable of inducing ICAM-1 expression selectively in the pulmonary artery. ICAM-1 likely plays a significant role in the observed inflammatory cell recruitment, specifically to vascular lesions in the pulmonary artery and not the pulmonary microcirculation.
Insights
In pulmonary arterial hypertension (PAH), late-stage microparticles (MPs) selectively increase ICAM-1 in pulmonary artery cells, not microcirculation. Endoglin-positive MPs drive this response, impacting inflammatory cell recruitment.
Area of Science:
- Cardiovascular Research
- Pulmonary Hypertension Pathophysiology
- Endothelial Cell Biology
Background:
- Microparticles (MPs) are known to stimulate inflammatory adhesion molecule expression in systemic vascular diseases.
- The effect of circulating MPs on localized intercellular adhesion molecule 1 (ICAM-1) expression in the distinct pulmonary endothelium during pulmonary arterial hypertension (PAH) remains unclear.
- Pulmonary vascular lesions in PAH involve inflammatory cell infiltration in arteries and arterioles, but not the microcirculation, suggesting a localized endothelial response.
Purpose of the Study:
- To investigate whether circulating MPs from a rat model of severe PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression.
- To determine if this ICAM-1 induction is specific to certain segments of the pulmonary circulation.
- To identify specific MP populations responsible for ICAM-1 stimulation.
Main Methods:
- Pulmonary artery endothelial cells (PAECs) and pulmonary microvascular endothelial cells (PMVECs) were exposed to MPs isolated from rats with early-stage (3-weeks) and late-stage (8-weeks) PAH.
- Flow cytometry and cell-based assays were used to measure ICAM-1 expression.
- Endoglin-positive (endoglin+) MPs were isolated and tested for their ability to induce ICAM-1.
Main Results:
- Late-stage PAH MPs significantly increased ICAM-1 in PAECs, whereas early-stage PAH MPs did not.
- Late-stage PAH MPs did not increase ICAM-1 expression in PMVECs, indicating selectivity for the pulmonary artery endothelium.
- Late-stage endoglin+ PAH MPs were sufficient to promote whole-cell ICAM-1 increases in PAECs, but not surface-only expression.
Conclusions:
- Circulating MPs from late-stage PAH selectively induce ICAM-1 expression in pulmonary artery endothelium, but not in the pulmonary microcirculation.
- Endoglin-positive MPs from late-stage PAH are sufficient to drive this selective ICAM-1 response.
- These findings suggest that MPs play a significant role in inflammatory cell recruitment to vascular lesions in the pulmonary artery during PAH.
