Table 2.
MMP-9 in patients with OSA.
| Study | Sample Size (men) | OSA Severity (n unless otherwise indicated) | MMP-9 ng/mL | Other Inflammatory Markers | Laboratory Method | Intervention | Results Summary |
|---|---|---|---|---|---|---|---|
| Wang et al,45 China | 47 (36) | Mild = 16; moderate = 12; severe = 19 | ↑ | N/A | Gelatin zymography | No | • Higher MMP-9 levels in patients with OSA correlated with HTN and LVH occurrence |
| • MMP-9 levels positively correlated with AHI, ODI, and MAP | |||||||
| • Risk factors for developing HTN in patients with OSA and without any cardiovascular dysfunction: OSA severity, nadir of oxygen saturation, and MMP-9 | |||||||
| Volna et al,106 Czech Republic | 51 (51) | Mean values: AHI = 31; ODI = 32; SpO2 = 93%; T90% = 15% | ↑ | MMP-2, copper, zinc, hsCRP, sRAGE | ELISA | No | • Strongest correlation between MMP-9, copper, and hsCRP and OSA parameters ODI and mean SpO2, which were higher in patients with severe OSA |
| • Strongest biological markers of oxidative stress in patients with OSA were copper and hsCRP, independent of BMI | |||||||
| • MMP-9 associated with OSA severity, based on ODI, mean SpO2, and T90% | |||||||
| • AHI positively correlated with hsCRP only | |||||||
| • sRAGE protective against oxidative stress in patients with OSA (associated with AHI and ODI) and negatively correlated with BMI | |||||||
| Maeder et al,47 Switzerland | 98 (71) | None/mild = 65; moderate/severe = 33 | No Δ | BNP; NT-proBNP; VEGF; IL-6; insulin | Erenna immunoassay** | Yes; CPAP 1 night | • Increased insulin levels before sleep |
| • Increased IL-6 levels after sleep | |||||||
| • No Δ in BNP, NT-proBNP, or VEGF in none/mild OSA compared with moderate/severe OSA | |||||||
| • No Δ in levels of all these markers after 1 night of CPAP use | |||||||
| Tazaki et al,49 Japan | 66 (66) no women | Control patients/patients who were obese = 18; mild = 24; moderate/severe = 24 | ↑ | TIMP-1; IL-6; TNF-α (2 sets of samples taken before and after sleep) | Gelatin zymography | Yes; CPAP 1 mo | • MMP-9 levels and activity higher in patients with OSA compared with control patients |
| • MMP-9 levels correlated with IL-6 and TNF-α levels in patients with OSA | |||||||
| • TIMP-1 levels did not change between patients with OSA and control patients | |||||||
| • OSA severity related to MMP-9 levels and activity | |||||||
| • Treatment with CPAP in patients with moderate/severe OSA improved MMP-9, IL-6, and TNF-α levels | |||||||
| • Treatment with CPAP did not affect TIMP-1 levels | |||||||
| • Positive correlation between MMP-9 levels and activity and duration of hypoxia in patients with OSA (ie, T90%) | |||||||
| Tamaki et al,50 Nara, Japan | 46 (42) | Control patients = 13; mild/moderate = 13; severe = 20 | ↑ | MCP-1; TNF-α (2 sets of samples taken before and after sleep) | ELISA | Yes; CPAP 3 mo | • MMP-9, MCP-1, and TNF-α levels increased in patients with severe OSA compared with control patients |
| • MMP-9, MCP-1, and TNF-α levels did not change significantly in patients with mild or moderate OSA compared with control patients | |||||||
| • TNF-α levels correlated with OSA severity | |||||||
| • Treatment with CPAP (3 months) decreased MMP-9, MCP-1, and TNF-α levels | |||||||
| Bonanno et al,52 Italy | 50 (50) no women | RDI < 30 = 25; RDI > 30 = 25; normotensive = 13; HTN = 13 | No Δ | Relaxin; TIMP-1; MMP-9/TIMP-1; MMP-2; TIMP-2; MMP-2/TIMP-2; VEGF | ELISA | No | • Relaxin did not differ between OSA patients who were normotensive and hypertensive suggesting that relaxin does not lay a role in OSA-induced hypertension |
| • MMP-9 and TIMP-1 did not differ between different degrees of OSA (however, there was a trend for increased MMP-9 in severe OSA, not statistically significant) | |||||||
| • MMP-2 was lower in patients with severe OSA | |||||||
| • Detectable relaxin levels not associated with higher VEGF levels | |||||||
| • VEGF positively correlated with MMP-9 | |||||||
| • VEGF levels higher in patients with severe OSA | |||||||
| Hopps et al,105 Italy | 79 (53) | Control patients = 31; mild = 21; severe = 27 | ↑ | TIMP-1; MMP-9/TIMP-1; MMP-2; TIMP-2; MMP-2/TIMP-2 | ELISA | No | • MMP-9, TIMP-1, MMP-2, and TIMP-2 elevated in patients with OSA compared with control patients |
| • MMP-9, TIMP-1, MMP-2, and TIMP-2 elevated more in severe OSA than in mild OSA | |||||||
| • MMP-9/TIMP-1 ratio decreased in patients with OSA compared with control patients | |||||||
| • MMP-9/TIMP-1 ratio decreased more in severe OSA than in mild OSA | |||||||
| • No significant variation in MMP-2/TIMP-2 ratio between OSA group and control group or between subgroups of OSA | |||||||
| • Positive correlation between MMP-9 and AHI | |||||||
| • Positive correlation between MMP-9 and ODI | |||||||
| • Negative correlation between MMP-9 and mean SpO2 | |||||||
| • Positive correlation between MMP-9 and neck circumference | |||||||
| Hopps et al46 | 48 (37) | Low grade group (mild and moderate) = 21; High grade group (severe) = 27 | ↑ | Gelatinases and their inhibitors: MMP-2, MMP-9, TIMP-1, TIMP-2; oxidative status; lipid peroxidation (TBARS); protein peroxidation (PC); TAS; NOx metabolites | ELISA | No | • Significant increase in lipid and protein peroxidation and decrease in NOx metabolites in H group compared with L group |
| • Significant increase in MMP-9 and TIMP-1 levels in H group compared with L group | |||||||
| • No significant difference in MMP-2 and TIMP-2 between H and L groups | |||||||
| • Correlations between MMPs, oxidative stress, and OSA parameters | |||||||
| • Positive correlation between MMP-9 and TBARS | |||||||
| • Positive correlation between MMP-2 and TAS | |||||||
| • Negative correlation between TIMP-1 and TBARS | |||||||
| • Positive correlation between MMP-9 and AHI and ODI but negative correlation with mean SpO2 | |||||||
| Chuang et al,107 Taiwan | 28 (28) no women | AI 0 = 11; AI 1–5 = 9; AI > 5 = 8 | ↑ | MMP-1; MMP-2; MMP-3; TIMP-1 (2 sets of samples taken before and after sleep) | ELISA; zymography (for MMP-9 activity); real-time PCR (for MMP-9 gene expression in monocytes) | No | • MMP-9 levels and activity increased in all groups, especially in patients with severe OSA |
| • MMP-9 levels correlated with OSA severity | |||||||
| • MMP-9 gene expression in monocytes correlated with OSA severity and MMP-9 levels | |||||||
| • MMP-1, MMP-2, MMP-3, and TIMP-1 did not change between OSA groups | |||||||
| Feng et al,108 China | 100 | Control patients= 50; OSA = 50 | ↑ | FFA | ELISA | No | • Both MMP-9 and FFA levels higher in patients with OSA compared with control patients |
| • Both MMP-9 and FFA levels in OSA together associated with higher cardiovascular risk compared with either one or the other alone | |||||||
| Vuralkan et al,51 Turkey | 25 (14) | Mean AHI = 17 (sleep studies and blood samples obtained before surgery [UPF] and 6 months after surgery) | ↑ | MDA | ELISA | Yes; UPF | • MMP-9 and MDA higher in patients with OSA before UPF surgery compared with postoperative levels |
| Nizam et al,48 Turkey | 50 (30) | Control patients = 13; mild/moderate = 17; severe = 20 | No Δ | MMP-8; TIMP-1; MMP-8/TIMP-1; pro-MMP-9; pro-MMP-2; NE; (serum and salivary levels) | ELISA; gelatin zymography; IFMA | No | • In serum samples, only pro-MMP-9 lower in patients with severe OSA compared with control patients; other MMPs did not show significant difference in the 3 groups |
| • In salivary samples, NE significantly lower in patients with mild-moderate and severe OSA compared with control patients | |||||||
| • Serum and salivary NE and pro-MMP-2 lower in patients with OSA compared with control patients | |||||||
| Ye al,109 China | 76 | Patients who were obese/control patients= 25; mild = 23; moderate-severe = 28 | ↑ | CRP | ELISA | No | • MMP-9 significantly higher in patients with moderate to severe OSA than in patients with mild OSA and mild OSA than patients who were obese and control patients |
| • CRP and MMP-9 positively moderately correlated with AHI even after adjusting for age and BMI | |||||||
| • CRP levels moderately correlated with levels of MMP-9 in patients with OSA |
BMI = body mass index, BNP = brain natriuretic peptide, ELISA = enzyme-linked immunosorbent assay, FFA = free fatty acids, hsCRP = high sensitivity C-Reactive Protein, HTN = hypertension, IFMA = immunofluorometric assays, LVH = left ventricular hypertrophy, MAP = mean arterial pressure, MCP-1 = monocyte chemoattractant protein-1, MDA = malondialdehyde, MMP = matrix metalloproteinase, NE = neutrophil elastase, NOx = nitric oxide metabolites, ODI = oxygen desaturation index, PC = protein carbonyl, PCR = polymerase chain reaction, RDI = Respiratory Disturbance Index, SPO2= oxygen saturation, sRAGE = soluble Receptor of Advanced Glycation end Products, TAS = total antioxidant status, TBARS = thiobarbituric acid-reactive substances, TIMP = tissue inhibitor of matrix metalloproteinase, TNF-α = tumor necrosis factor-alpha, T-90% = Time spent with SO2 < 90%, UPF = uvulopalatal flap, VEGF = vascular endothelial growth factor. **Erenna instruments - MilliporeSigma, Billerica, MA.