Concomitant elevations of MMP‐9, NGAL, proMMP‐9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease

Abstract

A growing body of evidence points towards smoking‐related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase‐9 (pro‐ and active MMP‐9), neutrophil gelatinase‐associated lipocalin (NGAL) and the proMMP‐9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable‐phase COPD patients (82 smokers, 18 never‐smokers) and 28 healthy adults (21 smokers, 7 never‐smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP‐9, NGAL and proMMP‐9/NGAL in COPD smokers. While the triad discriminated between smokers and non‐smokers in the COPD group, MMP‐9 and proMMP‐9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack‐years did not alter the findings. Serum MMP‐9, NGAL and proMMP‐9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP‐3 (but not of IL‐6 and MMP‐12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack‐years. Among COPD smokers, levels of MMP‐9, NGAL and proMMP‐9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP‐9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP‐9, NGAL, proMMP‐9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking.

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

“…In this study, we chose to measure urine extracellular urine mtDNA (u-mtDNA) levels, as it may serve as an indicator of systemic mitochondrial damage. Additionally, recent studies from our group and others provide evidence that individuals with COPD have a higher incidence of chronic kidney disease (CKD) (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) and that mitochondrial dysfunction may be one of the mechanisms behind this finding (56). Specifically, we have recently shown that exposure to cigarette smoke induces mitochondrial swelling and loss of cristae in murine renal tubular epithelial cells (56), and that glomerulosclerosis and tubulointerstitial fibrosis occur more frequently in patients with COPD than in control subjects (44).…”

Beclin-1 regulates cigarette smoke–induced kidney injury in a murine model of chronic obstructive pulmonary disease

“…A potential association between COPD and CKD prevalence has previously been suggested in several studies (6,12). COPD patients may exhibit an increased risk of lower estimated glomerular filtration rate (eGFR) (12), higher serum NGAL levels (57)(58)(59), and greater microalbuminuria (12,(60)(61)(62). Microalbuminuria has also been associated with a greater prevalence of hypoxemia (60), all-cause mortality (62), and acute exacerbations (63) in COPD patients.…”

MMP‐3 (–1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)‐3 and correlate with severity of COPD: A study of MMP‐3, MMP‐7 and MMP‐12 in a Tunisian population

“…A total of 216 healthy subjects and 138 COPD patients living in the central coast of Tunisia were recruited from the National Blood Transfusion Center and the Services of Pneumology and Physiology at the Farhat Hached Hospital (Sousse, Tunisia). Patients and controls underwent a pulmonary function test using a body plethysmography (ZAN 500 Body II; ZAN Messgerate GmbH, Oberthulba, Germany) as described previously . Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were the most important parameters measured.…”

“…Patients and controls underwent a pulmonary function test using a body plethysmography (ZAN 500 Body II; ZAN Messgerate GmbH, Oberthulba, Germany) as described previously. 22 Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were the most important parameters measured.…”