Serum MMP-9, SP-D, and VEGF levels reflect the severity of connective tissue disease-associated interstitial lung diseases

Abstract

Background Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD). This study aims to evaluate the clinical diagnostic value of matrix metalloproteinase-9 (MMP-9), surfactant protein-D (SP-D), and vascular endothelial growth factor (VEGF) as potential biomarkers for CTD-ILD. Methods This research included 33 CTD-ILD patients, 31 CTD patients without ILD, and 24 healthy control subjects. Then, the value of biomarkers for the diagnosis and evaluation of CTD-ILD was assessed through high-resolution computed tomography (HRCT) findings and pulmonary function test (PFT) parameters. Results The serum MMP-9, SP-D, and VEGF levels in the CTD-ILD group were higher than those in the CTD-NILD group and healthy group. The ROC curve indicates that VEGF has good to excellent diagnostic performance in diagnosing CTD-ILD, the cut-off that best optimizes sensitivity and specificity in diagnosing CTD-ILD is 277.60 pg/ml (sensitivity, 87.9%; specificity, 83.6%), with an area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.842–0.968); The ROC curve for MMP-9 suggests this biomarker is fair for diagnosis of CTD-ILD(sensitivity, 81.8%; specificity, 81.8%), with an AUC of 0.867 (95% CI 0.784–0.950), but SP-D only provided lower specificity with higher sensitivity in diagnosing CTD-ILD(sensitivity, 90.9%; specificity, 40.0%). The different serum biomarkers are more specific and sensitive when combined to diagnose ILD. The semiquantitative score for the degree of ILD severity on HRCT was positively correlated with SP-D and VEGF levels (r = 0.461, P = 0.007; r = 0.362, P = 0.039), and serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. The percentage of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted) had a negative correlation with the SP-D level (r = − 0.407, P = 0.044) and a statistically negative correlation between MMP-9 and the forced vital capacity (FVC) (r = − 0.451, P = 0.024). Conclusions Serum MMP-9, SP-D, and VEGF levels may have clinical value in screening and evaluating the severity of CTD-ILD.

Vascular endothelial growth factor in hypersensitivity pneumonitis and connective tissue disease-associated interstitial lung disease

“…Our results showed that there was no statistically significant relationship between serum VEGF levels and radiological findings, while De Santis et al [16] reported that among systemic sclerosis cases, serum VEGF was directly correlated with ground glass and reticular pattern extent on HRCT, and Lv et al [5] showed that VEGF levels were positively correlated with CTD-ILD severity by HRCT.…”

“…VEGF is believed to contribute in the progression of connective tissue disease-associated interstitial lung diseases (CTD-ILD), as it plays a dual role in encouraging and inhibiting pulmonary fibrosis. Also, VEGF subtype expression imbalance can contribute to the development of the disease, in which proliferation of endothelial cells and fibroblasts can be induced by VEGF [5]. Our aim was to compare serum VEGF level in HP and CTD-ILD patients in relation to control and to assess the relationship between serum level of VEGF, functional severity, and presence of pulmonary hypertension.…”

Identifying the link between serum VEGF and KL-6 concentrations: a correlation analysis for idiopathic pulmonary fibrosis interstitial lung disease progression

“…For idiopathic pulmonary fibrosis interstitial lung disease (IPF-ILD), recent studies have revealed potential mechanisms and biomarkers associated with disease progression (5)(6)(7)(8)(9)(10). Among them, vascular endothelial growth factor (VEGF), a key angiogenic factor, promotes neovascularization, increases vascular permeability, and regulates the expression of cytokines associated with fibrosis, thus driving the progression of IPF-ILD (11).…”

The effects of lipoic acid on respiratory diseases

“…Recent studies have demonstrated that matrix metalloproteinases (MMPs), which are pivotal proteolytic enzymes, are involved in pathological and inflammatory processes in several respiratory diseases, such as interstitial pneumonia [237] , pulmonary fibrosis [238] , and COPD [239] . In particular, MMP-1, MMP-2, MMP-8, and TIMP-1 have been demonstrated in experimental and clinical research to influence inflammation [240] , [241] , [242] .…”