Impact of Matrix Metalloproteinase-9 during Periodontitis and Cardiovascular Diseases.
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ABSTRACT:
SUBMITTER: Isola G
PROVIDER: S-EPMC8004886 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Matrix metalloproteinases (MMPs) are a family of host-derived proteinases reported to mediate multiple functions associated with periodontal breakdown and inflammation. High MMP levels in African-American children with localized aggressive periodontitis (LAgP) have been reported previously by the present authors. However, little is known about MMP reductions in gingival crevicular fluid (GCF) after therapy. This study aims to evaluate MMP levels in the GCF after treatment of LAgP and to correlate these levels with clinical response.GCF samples were collected from 29 African-American individuals diagnosed with LAgP. GCF was collected from one diseased site (probing depth [PD] >4 mm, bleeding on probing [BOP], and clinical attachment level ? 2 mm) and one healthy site (PD ? 3 mm, no BOP) from each individual at baseline and 3 and 6 months after periodontal treatment, which consisted of full-mouth scaling and root planing (SRP) and systemic antibiotics. The volume of GCF was controlled using a calibrated gingival fluid meter, and levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 were assessed using fluorometric kits.MMP-1, MMP-8, MMP-9, MMP-12, and MMP-13 levels were reduced significantly up to 6 months, comparable to healthy sites at the same point. Significant correlations were noted between MMP-2, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-13 levels and percentage of sites with PD >4 mm. MMP-3, MMP-12, and MMP-13 levels also correlated with mean PD of affected sites.Treatment of LAgP with SRP and systemic antibiotics was effective in reducing local levels of specific MMPs in African-American individuals, which correlated positively with some clinical parameters.
| S-EPMC4418528 | biostudies-literature
Project description:BACKGROUND:In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS:There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.
| S-EPMC7027895 | biostudies-literature
Project description:Background:In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. Material and Methods:There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations. Results and Conclusions:The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.
| S-EPMC7218770 | biostudies-literature
Project description:Periodontitis is a multifactorial inflammatory disease, pathogenic bacteria being the primary etiological agents. The host response and the severity of clinical manifestation are determined by genetic and environmental factors. There is some evidence that the individual response to environmental variations in the immune response in periodontitis is associated with genetic factors. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes located in the extracellular matrix. Their primary function is the breakdown of connective tissue components. Their role in the oral cavity is very vital. In this literature review, we summarized the contemporary knowledge on the function of MMPs in oral cavity and periodontal disease.
| S-EPMC7595482 | biostudies-literature
Project description:AimPeriodontitis is a chronic inflammatory disease, characterized by irreversible destruction of tooth-supporting tissue including alveolar bone. We recently reported mucin 4 (MUC4) and matrix metalloproteinase 7 (MMP7) as highly associated with periodontitis in gingival tissue biopsies. The aim of this study was to further investigate the levels of MUC4 and MMP7 in saliva and gingival crevicular fluid (GCF) samples of patients with periodontitis.Materials and methodsSaliva and GCF samples were collected from periodontitis patients and healthy controls. The levels of MUC4, MMP7, and total protein concentrations were analysed using ELISA or Bradford assay.ResultsMUC4 levels were significantly lower in saliva and GCF from periodontitis patients relative to healthy controls. MMP7 levels were significantly higher in saliva and GCF from periodontitis patients. Multivariate analysis revealed that MUC4 was significantly associated with periodontitis after adjusting for age and smoking habits and, moreover, that the combination of MUC4 and MMP7 accurately discriminated periodontitis from healthy controls.ConclusionsMUC4 and MMP7 may be utilized as possible novel biomarkers for periodontitis.
| S-EPMC5347886 | biostudies-literature
Project description:The goal of the study was to assess the relationship between cardioprotective medications, i.e., beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), statins, acetylsalicylic acid (ASA), and periodontitis (PD). Xerostomia increases the risk of PD and is a side effect of some pharmacotherapies. Information about the effect of cardioprotective treatment of periodontal status is scarce. We studied 562 dentate residents of Krakow at the age of 50 to 70 years. Information about treatment was collected using a standardized questionnaire. The pocket depth and clinical attachment level (CAL) were used to ascertain PD. Multivariate logistic regression was applied to assess the relation between cardioprotective medications and PD. PD was found in 74% of participants. The range of cardioprotective drug use among participants was 7% (ARBs) to 32% (beta-blockers). After adjusting for age, sex, number of teeth, smoking, and education, ASA's use was related to a lower prevalence of PD in all dentate participants (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.40-0.99). The use of ARBs and statins was found to be associated with a higher prevalence of PD in persons having ≥6 teeth (odds ratio (OR) = 3.57, 95% CI: 1.06-11.99 and OR = 1.81, 95% CI: 1.03-3.16, respectively). Further adjustment for CVD risk factors, history of coronary heart disease, and other chronic diseases did not attenuate the results. There was no significant relation between PD and the use of other cardioprotective drugs.
| S-EPMC7831110 | biostudies-literature
Project description:Members of the matrix metalloproteinase (MMP) family selectively cleave collagens in vivo. However, the substrate structural determinants that facilitate interaction with specific MMPs are not well defined. We hypothesized that type I-III collagen sequences located N- or C-terminal to the physiological cleavage site mediate substrate selectivity among MMP-1, MMP-2, MMP-8, MMP-13, and MMP-14/membrane-type 1 (MT1)-MMP. The enzyme kinetics for hydrolysis of three fluorogenic triple-helical peptides (fTHPs) was evaluated herein. The first fTHP contained consensus residues 769-783 from type I-III collagens, the second inserted ?1(II) collagen residues 763-768 N-terminal to the consensus sequence, and the third inserted ?1(II) collagen residues 784-792 C-terminal to the consensus sequence. Our analyses showed that insertion of the C-terminal residues significantly increased k(cat)/K(m) and k(cat) for MMP-1. MMP-13 showed the opposite behavior with a decreased k(cat)/K(m) and k(cat) and a greatly improved K(m) in response to the C-terminal residues. Insertion of the N-terminal residues enhanced k(cat)/K(m) and k(cat) for MMP-8 and MT1-MMP. For MMP-2, the C-terminal residues enhanced K(m) and dramatically decreased k(cat), resulting in a decrease in the overall activity. These changes in activities and kinetic parameters represented the collagen preferences of MMP-8, MMP-13, and MT1-MMP well. Thus, interactions with secondary binding sites (exosites) helped direct the specificity of these enzymes. However, MMP-1 collagen preferences were not recapitulated by the fTHP studies. The preference of MMP-1 for type III collagen appears to be primarily based on the flexibility of the hydrolysis site of type III collagen compared with types I and II. Further characterization of exosite determinants that govern interactions of MMPs with collagenous substrates should aid the development of pharmacotherapeutics that target individual MMPs.
| S-EPMC3199499 | biostudies-literature
Project description:Matrix metalloproteinase-3 (MMP3) plays a key role in tissue degradation in periodontitis. The relationship between the MMP3 -1171 5A/6A polymorphism (rs35068180) and periodontitis has been widely studied. However, existing studies have yielded contradictory results. We therefore conducted a meta-analysis to comprehensively investigate these inconclusive findings. Several electronic databases were searched for eligible articles. Seven case-control studies from 6 articles were searched without any language restrictions. Pooled estimates indicated that MMP3 -1171 5A/6A polymorphism is associated with a decreased risk of periodontitis (allelic genetic model: OR?=?0.70, 95% CI: 0.62-0.80, P(heterogeneity)?=?0.315; heterozygous model: OR?=?0.50, 95% CI: 0.39-0.65, P(heterogeneity)?=?0.221; homozygous model: OR?=?0.42, 95% CI: 0.25-0.69, P(heterogeneity)?=?0.265; dominant model: OR?=?0.49, 95% CI: 0.38-0.62, P(heterogeneity)?=?0.238, respectively). Similar results were also found in chronic periodontitis (CP), Asian, Asian&CP, and non-smokers subgroups. Moreover, MMP3 rs35068180 polymorphism might be associated with a lower risk of aggressive periodontitis (AgP) in Asians (allelic genetic model: OR?=?0.66, 95% CI: 0.48-0.91, P(heterogeneity)?=?0.945), and CP in Caucasians and Brazilians. In conclusion, this meta-analysis demonstrates that MMP3 -1171 5A/6A polymorphism may be associated with decreased risk of both CP and AgP in Asians. Large independent studies to replicate these results are necessary to validate these associations in other populations.
| S-EPMC4485030 | biostudies-literature
Project description:We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Science was conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6 polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/T polymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/T polymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis.
| S-EPMC4837403 | biostudies-other
Project description:Matrix metalloproteinase-7 (MMP-7) is a secreted zinc-dependent endopeptidase that is implicated in regulating kidney homeostasis and diseases. MMP-7 is produced as an inactive zymogen, and proteolytic cleavage is required for its activation. MMP-7 is barely expressed in normal adult kidney but upregulated in acute kidney injury (AKI) and chronic kidney disease (CKD). The expression of MMP-7 is transcriptionally regulated by Wnt/β-catenin and other cues. As a secreted protein, MMP-7 is present and increased in the urine of patients, and its levels serve as a noninvasive biomarker for predicting AKI prognosis and monitoring CKD progression. Apart from degrading components of the extracellular matrix, MMP-7 also cleaves a wide range of substrates, such as E-cadherin, Fas ligand, and nephrin. As such, it plays an essential role in regulating many cellular processes, such as cell proliferation, apoptosis, epithelial-mesenchymal transition, and podocyte injury. The function of MMP-7 in kidney diseases is complex and context-dependent. It protects against AKI by priming tubular cells for survival and regeneration but promotes kidney fibrosis and CKD progression. MMP-7 also impairs podocyte integrity and induces proteinuria. In this review, we summarized recent advances in our understanding of the regulation, role, and mechanisms of MMP-7 in the pathogenesis of kidney diseases. We also discussed the potential of MMP-7 as a biomarker and therapeutic target in a clinical setting.
| S-EPMC7356035 | biostudies-literature