Journal article
Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study
Annals of the American Thoracic Society, Vol.21(6), pp.884-894
06/2024
DOI: 10.1513/AnnalsATS.202305-417OC
PMCID: PMC11160125
PMID: 38335160
Abstract
Rationale Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. Molecular mechanisms underlying these changes are poorly understood in patients due, in part, to the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMC) interact with the pulmonary endothelium. Objective To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with 10 or more pack-years. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume (PMBV), and mean transit time were assessed on contrast-enhanced MRI, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with PMBV measures on contrast-enhanced, dual-energy CT. Differential expression analyses were adjusted for age, gender, race-ethnicity, educational attainment, height, weight, smoking status, and pack-years. Results The 79 participants in the discovery sample had mean age of 69±6 years, 44% were female, 25% were non-white, 34% were current smokers and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with MRI (n=47) or dual-energy CT scan (n=157) measures. Many of the identified genes are involved in inflammatory processes, including NF-κB and chemokine signaling pathways. Conclusions PBMC gene expression in NF-κB, inflammatory and chemokine signaling pathways was associated pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.
Details
- Title: Subtitle
- Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study
- Creators
- Kristina L BuschurTess D Pottinger - Columbia University Irving Medical CenterJens Vogel-Claussen - Johns Hopkins University School of MedicineCharles A Powell - Mount Sinai Medical CenterFrancois Aguet - Broad InstituteNorrina B Allen - Northwestern UniversityKristin Ardlie - Broad InstituteDavid A Bluemke - University of Wisconsin–MadisonPeter Durda - University of VermontEmilia A Hermann - Columbia University Irving Medical CenterEric A Hoffman - University of Iowa Carver College of Medicine, Radiology, Iowa City, Iowa, United StatesJoão A C Lima - Johns Hopkins UniversityYongmei Liu - Duke University School of MedicineDaniel Malinsky - Columbia UniversityAni Manichaikul - University of VirginiaAmin Motahari - University of IowaWendy S Post - Johns Hopkins UniversityMartin R Prince - Columbia University Irving Medical CenterStephen S Rich - University of VirginiaJerome I Rotter - The Lundquist InstituteBenjamin M Smith - McGill University Health CentreRussell P Tracy - University of VermontKarol Watson - University of California, Los AngelesHinrich B Winther - Medizinische Hochschule HannoverTuuli Lappalainen - KTH Royal Institute of TechnologyR Graham Barr - Columbia University Irving Medical Center
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.21(6), pp.884-894
- DOI
- 10.1513/AnnalsATS.202305-417OC
- PMID
- 38335160
- PMCID
- PMC11160125
- NLM abbreviation
- Ann Am Thorac Soc
- ISSN
- 2329-6933
- eISSN
- 2325-6621
- Language
- English
- Electronic publication date
- 02/09/2024
- Date published
- 06/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984557959002771
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