COPD Patients Exhibit Distinct Gene Expression, Accelerated Cellular Aging, and Bias to M2 Macrophages

COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate,...

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Published in:International journal of molecular sciences 2023-06, Vol.24 (12), p.9913
Main Authors: da Silva, Camila Oliveira, de Souza Nogueira, Jeane, do Nascimento, Adriana Paulino, Victoni, Tatiana, Bártholo, Thiago Prudente, da Costa, Cláudia Henrique, Costa, Andrea Monte Alto, Valença, Samuel Dos Santos, Schmidt, Martina, Porto, Luís Cristóvão
Format: Article
Language:English
Subjects:
Aging
Air flow
Airway management
Asthma
Brazil
Chronic obstructive pulmonary disease
Cytokines
Development and progression
DNA methylation
Emphysema
Enzymes
Epigenetics
Gene expression
Genes
HDAC2 protein
Health aspects
Histone deacetylase
Histones
Immune response
Inflammation
Life Sciences
Macrophages
Massachusetts
Morbidity
Mortality
Oxidative stress
Patients
Phenotypes
Pulmonary fibrosis
Smokers
Telomeres
Transcription factors
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Summary:COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24129913