Association of matrix metalloproteinase-9 and nitric oxide with hypertension in obstructive sleep apnea.
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ABSTRACT: Background
Patients with obstructive sleep apnea (OSA) are more likely to suffer from hypertension. At the same time, the serum levels of matrix metalloproteinase-9 (MMP-9) and nitric oxide (NO) in patients with OSA are also changed in OSA patients. We investigated the correlation between serum levels of MMP-9, NO in patients with OSA and their association with hypertension in those patients, and the effects of continuous positive airway pressure therapy (CPAP) on these serum biomarkers and blood pressure.Methods
Serum MMP-9 and NO levels and blood pressure of 57 patients with newly diagnosed OSA and 30 controls were measured; among them, 30 patients with moderate to severe OSA underwent 3-month CPAP treatment.Results
In comparison to the control group, the MMP-9 serum levels were higher (232.8 ± 103.2 ng/ml versus 161.6 ± 56.5 ng/ml, p < .001*), there was no statistical significance difference among serum NO (26.7 ± 9.1 IU/ml versus 31.0 ± 11.7 IU/ml, p = .06), and MMP-9 was negatively correlated to NO, especially in patients with hypertension (r = -.644, p = .02*). MMP-9, NO, and blood pressure were significantly recovered in the patients with OSA after CPAP treatment for 3 months (p < .05*).Conclusion
The MMP-9 level and the NO level were altered in OSA patients. The relationship between the two especially in patients with hypertension suggests the potential mechanism of OSA-induced hypertension.
SUBMITTER: Zeng S
PROVIDER: S-EPMC9194974 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Association of matrix metalloproteinase-9 and nitric oxide with hypertension in obstructive sleep apnea.
Zeng Shiying S Li Shisheng S Tang Qinglai Q Tuerdi Ayinuer A Tong Xinying X Tang Xiaojun X Yin Danhui D Li Mengmeng M Yang Qian Q
Laryngoscope investigative otolaryngology 20220425 3
<h4>Background</h4>Patients with obstructive sleep apnea (OSA) are more likely to suffer from hypertension. At the same time, the serum levels of matrix metalloproteinase-9 (MMP-9) and nitric oxide (NO) in patients with OSA are also changed in OSA patients. We investigated the correlation between serum levels of MMP-9, NO in patients with OSA and their association with hypertension in those patients, and the effects of continuous positive airway pressure therapy (CPAP) on these serum biomarkers ...[more]
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Project description:ObjectiveAirway inflammation plays an important role in obstructive sleep apnea (OSA); exhaled nitric oxide is regarded as a noninvasive marker of airway inflammation. The aim of this study was to evaluate fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) in patients with OSA.MethodsSeventy-five patients with OSA and 30 health controls were enrolled in this study. FeNO and nNO were measured before and after sleep. Nasal lavage was performed in 31 non-smoking individuals immediately after NO measurement in the morning. The sample of nasal lavage was taken for cell classification and analyzing interleukin 6 (IL-6) and interleukin 8 (IL-8).ResultsBoth FeNO and nNO were significantly higher in OSA (before sleep FeNO 21.08 ± 8.79 ppb vs.16.90 ± 6.86 ppb, p = 0.022; after sleep FeNO 25.57 ± 15.58 ppb vs.18.07 ± 6.25 ppb, p = 0.003; before sleep nNO 487.03 ± 115.83 ppb vs. 413.37 ± 73.10 ppb, p = 0.001; after sleep nNO 550.07 ± 130.24 ppb vs. 460.43 ± 109.77 ppb, p < 0.001). Furthermore, in non-smoking OSA, nNO levels were positively correlated with apnea hypopnea index (AHI) and average decrease of pulse arterial oxygen saturation (SpO2); after sleep, nNO was also positively associated to recording time with SpO2 < 90% and negatively associated to minimum SpO2. Both before and after sleep nNO levels were positively correlated with the percentage of neutrophils in nasal lavage (r = 0.528, p = 0.014; r = 0.702, p < 0.001, respectively). Additionally, before sleep nNO was also positively associated with IL-6 (r = 0.586, p = 0.005) and IL-8 (r = 0.520, p = 0.016) concentration.ConclusionThis study sustains the presence of airway inflammation in OSA patients with the increase of FeNO and nNO. The data suggests nNO might have greater value than FeNO since it positively correlated with OSA severity, and nNO is a potential bio-marker of nasal inflammation in non-smoking OSA patients.
| S-EPMC6700235 | biostudies-literature
Project description:Background Sleep fragmentation induced by repetitive arousals is a hallmark of obstructive sleep apnea (OSA). Sleep fragmentation has been linked to hypertension in community-based studies, but it is unclear if this association is manifest in OSA. We aimed to explore whether frequent arousals from sleep modify the relationship between OSA and prevalent hypertension. Methods and Results A total of 10 102 patients with OSA and 1614 primary snorers were included in the study. Hypertension was defined on either direct blood pressure measures or diagnosis by a physician. Spontaneous, respiratory, and movement arousals were derived by polysomnography. Logistic regression models were used to estimate the associations between arousals and prevalent hypertension in patients with OSA and primary snorers. For every 10-unit increase of total arousal index, odds of hypertension significantly increased in both the total sample (odds ratio [OR], 1.08; 95% CI, 1.03-1.14; P=0.002) and patients with OSA (OR, 1.10; 95% CI, 1.04-1.16; P<0.001), but not in the primary snoring group. Total arousal index was significantly associated with systolic blood pressure and diastolic blood pressure in the total sample (β=0.05 and β=0.06; P<0.001) and in patients with (β=0.05 and β=0.06; P<0.01), but not in primary snorers. In addition, a greater influence of respiratory events with arousals than respiratory events without arousals on blood pressure in OSA was also noted. Results were independent of confounders, including apnea-hypopnea index and nocturnal hypoxemia. Conclusions We conclude that repetitive arousals from sleep are independently associated with prevalent hypertension in patients with OSA.
| S-EPMC9075207 | biostudies-literature
Project description:BackgroundObstructive sleep apnea (OSA) is associated with adverse and interdependent cognitive and cardiovascular consequences. Increasing evidence suggests that nitric oxide synthase (NOS) and endothelin family (EDN) genes underlie mechanistic aspects of OSA-associated morbidities. We aimed to identify single nucleotide polymorphisms (SNPs) in the NOS family (3 isoforms), and EDN family (3 isoforms) to identify potential associations of these SNPs in children with OSA.MethodsA pediatric community cohort (ages 5-10 years) enriched for snoring underwent overnight polysomnographic (NPSG) and a fasting morning blood draw. The diagnostic criteria for OSA were an obstructive apnea-hypopnea Index (AHI) >2/h total sleep time (TST), snoring during the night, and a nadir oxyhemoglobin saturation <92%. Control children were defined as non-snoring children with AHI <2/h TST (NOSA). Endothelial function was assessed using a modified post-occlusive hyperemic test. The time to peak reperfusion (Tmax) was considered as the indicator for normal endothelial function (NEF; Tmax<45 sec), or ED (Tmax ≥ 45 sec). Genomic DNA from peripheral blood was extracted and allelic frequencies were assessed for, NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), endothelin receptor A, EDNRA, (27 SNPs), and endothelin receptor B, EDNRB (23 SNPs) using a custom SNPs array. The relative frequencies of NOS-1,-2, and -3, and EDN-1,-2,-3,-EDNRA, and-EDNRB genotypes were evaluated in 608 subjects [128 with OSA, and 480 without OSA (NOSA)]. Furthermore, subjects with OSA were divided into 2 subgroups: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). Linkage disequilibrium was analyzed using Haploview version 4.2 software.ResultsFor NOSA vs. OSA groups, 15 differentially distributed SNPs for NOS1 gene, and 1 SNP for NOS3 emerged, while 4 SNPs for EDN1 and 1 SNP for both EDN2 and EDN3 were identified. However, in the smaller sub-group for whom endothelial function was available, none of the significant SNPs was retained due to lack of statistical power.ConclusionsDifferences in the distribution of polymorphisms among NOS and EDN gene families suggest that these SNPs could play a contributory role in the pathophysiology and risk of OSA-induced cardiovascular morbidity. Thus, analysis of genotype-phenotype interactions in children with OSA may assist in the formulation of categorical risk estimates.
| S-EPMC3844410 | biostudies-literature
Project description:BackgroundExhaled nitric oxide (eNO) has been proposed as a noninvasive measure of airway inflammation. However, its value in patients with obstructive sleep apnea (OSA) is still controversial. The authors aim to assess the difference in eNO levels between patients with OSA and controls by a meta-analysis.MethodsA systematic search was performed in the PubMed, EMBASE, the Cochrane Library, and MEDLINE databases to collect relevant studies published from 1996 to 2016. Eligible studies that reported eNO levels in patients with OSA were included. STATA (version 12.0) was used for data analysis.ResultsTwo hundred eighty-four studies were reviewed for inclusion, with 16 studies pooled for analysis (16 studies for fractional exhaled nitric oxide [FENO], 5 for alveolar nitric oxide [CANO], and 4 for the maximum airway wall flux of nitric oxide [J'awNO]). The FENO levels were significantly higher in patients with OSA compared with that in the control groups (6.32 ppb, 95% confidence interval [CI] 4.46-8.33, P < 0.001). Furthermore, FENO was significantly increased (4.00 ppb, 95% CI 1.74-6.27, P = 0.001) after overnight sleep in patients with OSA, but not in healthy controls. Additionally, long-term continuous positive airway pressure (CPAP) therapy reduced FENO levels (-5.82 ppb, 95% CI -9.6 to -2.01, P < 0.001). However, the CANO (-0.01 ppb, 95% CI -1.66 to 1.64, P = 0.989) and J'awNO levels (220.32 pl/s, 95% CI -49.31 to 489.94, P = 0.109) were not significantly different between the OSA groups and non-OSA groups.ConclusionThe results of the meta-analysis suggest that OSA is significantly associated with airway inflammation and elevated FENO levels can be modified by long-term CPAP therapy. J'awNO and CANO levels were not significantly different between the OSA groups and control groups.
| S-EPMC5371487 | biostudies-literature
Project description:Systemic hypertension is prevalent among patients with obstructive sleep apnea (OSA). Short-term studies indicate that continuous positive airway pressure (CPAP) therapy reduces blood pressure in patients with hypertension and OSA.To determine whether CPAP therapy is associated with a lower risk of incident hypertension.A prospective cohort study of 1889 participants without hypertension who were referred to a sleep center in Zaragoza, Spain, for nocturnal polysomnography between January 1, 1994, and December 31, 2000. Incident hypertension was documented at annual follow-up visits up to January 1, 2011. Multivariable models adjusted for confounding factors, including change in body mass index from baseline to censored time, were used to calculate hazard ratios (HRs) of incident hypertension in participants without OSA (controls), with untreated OSA, and in those treated with CPAP therapy according to national guidelines.Incidence of new-onset hypertension.During 21,003 person-years of follow-up (median, 12.2 years), 705 cases (37.3%) of incident hypertension were observed. The crude incidence of hypertension per 100 person-years was 2.19 (95% CI, 1.71-2.67) in controls, 3.34 (95% CI, 2.85-3.82) in patients with OSA ineligible for CPAP therapy, 5.84 (95% CI, 4.82-6.86) in patients with OSA who declined CPAP therapy, 5.12 (95% CI, 3.76-6.47) in patients with OSA nonadherent to CPAP therapy, and 3.06 (95% CI, 2.70-3.41) in patients with OSA and treated with CPAP therapy. Compared with controls, the adjusted HRs for incident hypertension were greater among patients with OSA ineligible for CPAP therapy (1.33; 95% CI, 1.01-1.75), among those who declined CPAP therapy (1.96; 95% CI, 1.44-2.66), and among those nonadherent to CPAP therapy (1.78; 95% CI, 1.23-2.58), whereas the HR was lower in patients with OSA who were treated with CPAP therapy (0.71; 95% CI, 0.53-0.94).Compared with participants without OSA, the presence of OSA was associated with increased adjusted risk of incident hypertension; however, treatment with CPAP therapy was associated with a lower risk of hypertension.
| S-EPMC4657563 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Several studies have recently investigated the contribution of genetic factors in obstructive sleep apnea (OSA). Patients with OSA suffer from a reduction in nitric oxide (NO) serum level. This study investigated rs841, A930G p22phox, and rs1799983 polymorphisms in three critical genes involved in NO formation. A total of 94 patients with OSA and 100 healthy controls were enrolled into the study. Results showed there was no association between rs841, A930G p22phox and rs1799983 polymorphism and the risk of OSA (P = 0.51, P = 0.4 and P = 0.33, respectively). Moreover, rs841 GA genotype had a reverse relationship with the severity of OSA (P = 0.005). On the other hand, rs841 GA and A930G p22phox AA genotypes had a protective effect on daytime sleepiness in OSA patients (P = 0.01and P = 0.02, respectively). Additionally, the combination of rs841 and A930G p22phox (AG/AG and AG/AA) genotypes was significantly associated with a reduction in daytime sleepiness in OSA patients (P = 0.03 and P = 0.03, respectively). According to the results of our study, GA genotype of rs841 and GA/AA genotypes of A930G p22phox polymorphisms significantly reduced the severity of the problem and daytime sleepiness in OSA patients.
| S-EPMC6901474 | biostudies-literature
Project description:BackgroundObstructive sleep apnea (OSA) is a sleep disorder characterized as complete or partial upper airflow cessation during sleep. Although it has been widely accepted that OSA is a risk factor for the development of hypertension, the studies focusing on this topic revealed inconsistent results. We aimed to clarify the association between OSA and hypertension, including essential and medication-resistant hypertension.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. PubMed and Embase databases were used for searching the relevant studies published up to December 31, 2016. A quantitative approach of meta-analysis was performed to estimate the pooled odds ratio (OR) and 95% confidence interval (CI).ResultsTwenty-six studies with 51 623 participants (28 314 men, 23 309 women; mean age 51.8 years) met inclusion criteria and were included in this study. Among them, six studies showed a significant association between OSA and resistant hypertension (pooled OR = 2.842, 95% CI = 1.703-3.980, P < 0.05). Meanwhile, the combination of 20 original studies on the association of OSA with essential hypertension also presented significant results with the pooled ORs of 1.184 (95% CI = 1.093-1.274, P < 0.05) for mild OSA, 1.316 (95% CI = 1.197-1.433, P < 0.05) for moderate OSA and 1.561 (95% CI = 1.287-1.835, P < 0.05) for severe OSA.ConclusionsOur findings indicated that OSA is related to an increased risk of resistant hypertension. Mild, moderate and severe OSA are associated essential hypertension, as well a dose-response manner relationship is manifested. The associations are relatively stronger among Caucasians and male OSA patients.
| S-EPMC5825975 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:Importance:While much has been reported on the relationship between floppy eyelid syndrome and obstructive sleep apnea (OSA), the diagnostic criteria of floppy eyelid syndrome are often subjective and vague. Objective:To evaluate the association between OSA and quantitative markers of eyelid laxity or secondary ocular surface disease in a sleep clinic population. Design, Setting, and Participants:This investigation was a cross-sectional observational study at the Center for Sleep Medicine at Icahn School of Medicine at Mount Sinai. Participants were individuals referred for overnight polysomnography from March 1 to August 30, 2015. Main Outcomes and Measures:Eyelid laxity and ocular surface disease were assessed on bedside ophthalmologic examination. The presence and severity of OSA were determined from polysomnography results. Initial correlation between OSA and ocular surface and eyelid markers was calculated through bivariate linear regression analysis, and the association between ocular symptoms was obtained through bivariate ordered logistic regression. Analysis was repeated adjusting for known associations between OSA and sex, age, body mass index, and medical comorbidities through multivariable analysis. Results:In total, 201 individuals (402 eyes) were enrolled in the study. Their mean (SD) age was 53.2 (13.5) years, 43.3% (n?=?87) were female, 56.7% (n?=?114) were of white race/ethnicity, 26.9% (n?=?54) were black/African American, 4.0% (n?=?8) were Asian, 8.0% (n?=?16) were multiracial or other, and 4.5% (n?=?9) were of unknown race/ethnicity, with 21.9% (n?=?44) of all individuals self-identifying as Hispanic and 75.1% (n?=?151) self-identifying as non-Hispanic. After adjustment, no association was observed between OSA severity and an eyelid laxity score (regression coefficient, 0.85; 95% CI, -0.33 to 0.62; P?=?.40) or an ocular surface score (regression coefficient, 1.09; 95% CI, -0.32 to 0.29; P?=?.93). Through subset analysis, male sex was associated with a higher ocular surface score, while older age and diabetes were associated with a higher eyelid laxity score. Only one patient (0.5%) exhibited findings of floppy eyelid syndrome. Conclusions and Relevance:Among individuals referred for overnight polysomnography, quantitative markers of eyelid laxity were not associated with the presence or severity of OSA. Subset analysis suggests that prior studies may have been limited by confounding variables or the technique of identifying eyelid laxity.
| S-EPMC5710483 | biostudies-other