muramidase and Cardiovascular-Diseases

Metabolic syndrome and type 2 diabetes (T2DM) resulting from sustained hyperglycemia are considered as risk factors for cardiovascular disease (CVD) but the mechanism for their contribution to cardiopathogenesis is not well understood. Hyperglycemia induces nonenzymatic glycation of protein-yielding advanced glycation end products (AGE), which are postulated to stimulate interleukin-6 (IL-6) expression, triggering the liver to secrete tissue necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) that contribute to CVD pathogenesis. Although the high prevalence of periodontitis among individuals with diabetes is well known by dental researchers, it is relatively unrecognized in the medical community. The expression of the same proinflammatory mediators implicated in hyperglycemia (i.e., IL-6, TNF-alpha, and CRP) have been reported to be associated with periodontal disease and increased risk for CVD. We will review published evidence related to these 2 pathways and offer a consensus.

Topics: Carbohydrate Metabolism; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Focal Infection, Dental; Glycation End Products, Advanced; Humans; Hyperglycemia; Inflammation Mediators; Metabolic Syndrome; Muramidase; Periodontitis; Salivary Proteins and Peptides

Streptococcus mutans, a major pathogen of dental caries, is also known as a causative agent of cardiovascular disease. A 120 kDa collagen-binding protein (Cnm) of S. mutans is an important contributor to the pathogenicity of cardiovascular disease. Although dead bacteria have been detected in cardiovascular specimens by molecular biological methods, the pathogenicity of the bacteria remains unknown. Here, we analyzed the pathogenicity of killed S. mutans by focusing on collagen-binding ability and the effects on silkworms. In live S. mutans, Cnm-positive S. mutans had high collagen-binding activity, while Cnm-negative S. mutans had no such activity. After treatment with killed Cnm-positive S. mutans, amoxicillin-treated bacteria still had collagen-binding ability, while lysozyme-treated bacteria lost this ability. When live and amoxicillin-treated S. mutans strains were administered to silkworms, the survival rates of the silkworms were reduced; this reduction was more pronounced in Cnm-positive S. mutans infection than in Cnm-negative S. mutans infection. However, the administration of any of the lysozyme-treated bacteria did not reduce the survival rate of the silkworms. These results suggest that amoxicillin-killed Cnm-positive S. mutans strains maintain collagen-binding properties and pathogenicity in the silkworm model, and are possibly associated with pathogenicity in cardiovascular diseases.

Topics: Adhesins, Bacterial; Amoxicillin; Animals; Bombyx; Cardiovascular Diseases; Carrier Proteins; Collagen; Dental Caries; Disease Models, Animal; Humans; Muramidase; Saliva; Streptococcal Infections; Streptococcus mutans; Virulence

Understanding the interplay between adiposity, inflammation, and cardiovascular complications in type 2 diabetes mellitus (T2DM) remains a challenge. Signaling from adipocytes is considered important in this context. Adiponectin is the most abundant adipocytokine and has been associated with various measures of cardiovascular disease (CVD). This study examines the relationships between genetic variants in the adiponectin (ADIPOQ) and adiponectin-related signaling pathway genes and measures of subclinical CVD (vascular calcified plaque and carotid intima-media thickness), plasma lipids, and inflammation in T2DM.. Single-nucleotide polymorphisms (SNPs) in ADIPOQ (n = 45), SNPs tagging ADIPOR1 (n = 6), APIPOR2 (n = 8), APPL1 (n = 6) and known rare coding variants in KNG1 (n = 3) and LYZL1 (n = 3) were genotyped in 1220 European Americans from the family-based Diabetes Heart Study. Associations between SNPs and phenotypes of interest were assessed using a variance components analysis with adjustment for age, sex, T2DM-affected status, and body mass index.. There was minimal evidence of association between SNPs in the adiponectin signaling pathway genes and measures of calcified plaque; eight of the 71 SNPs showed evidence of association with subclinical CVD (P = 0.007-0.046) but not with other phenotypes examined. Nine additional SNPs were associated with at least one of the plasma lipid measures (P = 0.008-0.05).. Findings from this study do not support a significant role for variants in the adiponectin signaling pathway genes in contributing to risk for vascular calcification in T2DM. However, further understanding the interplay between adiposity, plasma lipids, and inflammation may prove important in the prediction and management of cardiovascular complications in T2DM.

Topics: Adaptor Proteins, Signal Transducing; Adiponectin; Aged; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Genotype; Humans; Inflammation; Lipids; Male; Middle Aged; Muramidase; Obesity; Phenotype; Plaque, Atherosclerotic; Polymorphism, Single Nucleotide; Receptors, Adiponectin; Signal Transduction; Tunica Intima; Tunica Media; Vascular Calcification; White People

Whereas circulating levels of C-reactive protein (CRP) have been associated with, for example, arterial stiffness, subclinical atherosclerosis and metabolic syndrome, other inflammatory biomarkers with potential interest for these conditions may not be measurable systemically. The predictive value of salivary biomarkers in these contexts has remained largely unexplored. The aim of the present study was to establish the association of different salivary biomarkers of inflammation with subclinical cardiovascular disease.. Two hundred and fifty-nine individuals were included in the study. Saliva and plasma samples were collected, and each individual underwent carotid ultrasound and measures of pulse wave velocity and blood pressure. Medical history of previous cardiovascular disease, current medications and smoking were collected by questionnaire.. Salivary levels of CRP, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), matrix metalloproteinase 9 (MMP-9), creatinine and lysozyme were measured. Salivary levels of CRP were significantly correlated with plasma levels (r = 0.73, P < 0.0001). In an age-adjusted and sex-adjusted analysis, salivary CRP was significantly and positively correlated with mean arterial blood pressure, pulse pressure, pulse wave velocity, BMI, metabolic syndrome, waist-to-hip ratio and intima-media thickness. Increasing age and sex-adjusted salivary CRP tertiles were in addition associated with carotid plaques. In a multivariate analysis, CRP and MMP-9 were associated with intima-media thickness, LTB4 and PGE2 with arterial stiffness, and lysozyme with hypertension.. Saliva may represent an alternative mean for evaluation of cardiovascular risk.

Topics: Aged; Atherosclerosis; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Creatinine; Dinoprostone; Female; Humans; Hypertension; Inflammation Mediators; Leukotriene B4; Male; Matrix Metalloproteinase 9; Metabolic Syndrome; Middle Aged; Muramidase; Pulse Wave Analysis; Risk Factors; Saliva; Vascular Stiffness; Waist-Hip Ratio

On the basis of the host-guest interactions between azobenzenes and cyclodextrins, a new strategy for the preparation of a dually functionalized poly(dimethylsiloxane) (PDMS) surface was investigated using surface-initiated atom-transfer radical polymerization (SI-ATRP) and click chemistry. The PDMS substrates were first oxidized in a H(2)SO(4)/H(2)O(2) solution to transform the surface Si-CH(3) groups into Si-OH groups. Then, the SI-ATRP initiator 3-(2-bromoisobutyramido)propyl(trime-thoxy)silane was grafted onto the substrates through a silanization reaction. Sequentially, the poly(ethylene glycol) (PEG) units were introduced onto the PDMS-Br surfaces via SI-ATRP reaction using oligo(ethylene glycol) methacrylate. Afterward, the bromide groups on the surface were converted to azido groups via nucleophilic substitution reaction with NaN(3). Finally, the azido-grafted PDMS surfaces were subjected to a click reaction with alkynyl and PEG-modified β-cyclodextrins, resulting in the grafting of cyclodextrins onto the PDMS surfaces. The composition and chemical state of the modified surfaces were characterized via X-ray photoelectron spectroscopy, and the stability and dynamic characteristics of the cyclodextrin-modified PDMS substrates were investigated via attenuated total reflection-Fourier transform infrared spectroscopy and temporal contact angle experiments. The surface morphology of the modified PDMS surfaces was characterized through imaging using a multimode atomic force microscope. A protein adsorption assay using Alexa Fluor594-labeled bovine serum albumin, Alexa Fluor594-labeled chicken egg albumin, and FITC-labeled lysozyme shows that the prepared PDMS surfaces possess good protein-repelling properties. On-surface studies on the interactions between azobenzenes and the cyclodextrin-modified surfaces reveal that the reversible binding of azobenzene to the cyclodextrin-modified PDMS surfaces and its subsequent release can be reversibly controlled using UV irradiation. Sandwich fluoroimmunoassay of the cardiac markers myoglobin and fatty acid-binding protein demonstrates that the cyclodextrin-modified PDMS surfaces can be repeatedly utilized in disease biomarker analysis.

Topics: Animals; Azo Compounds; beta-Cyclodextrins; Biomarkers; Cardiovascular Diseases; Cattle; Dimethylpolysiloxanes; Fatty Acid-Binding Proteins; Fluoroimmunoassay; Humans; Muramidase; Myoglobin; Organic Chemicals; Photoelectron Spectroscopy; Polyethylene Glycols; Serum Albumin, Bovine; Surface Properties

In septic shock, cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression and arterial vasodilation that develop in canine models of septic shock. To cause vasodilation, Lzm-S generates hydrogen peroxide (H(2)O(2)) that activates the smooth muscle soluble guanylate cyclase (sGC) pathway, although the mechanism of H(2)O(2) generation is not known. To cause myocardial depression, Lzm-S binds to the endocardial endothelium, resulting in the formation of nitric oxide (NO) and subsequent activation of myocardial sGC, although the initial signaling event is not clear. In this study, we examined whether the myocardial depression produced by Lzm-S was also caused by the generation of H(2)O(2) and whether Lzm-S could intrinsically generate H(2)O(2) as has been described for other protein types. In a canine ventricular trabecular preparation, we found that the peroxidizing agent Aspergillus niger catalase, that would breakdown H(2)O(2), prevented Lzm-S- induced decrease in contraction. We also found that compound I, a species of catalase formed during H(2)O(2) metabolism, could contribute to the NO generation caused by Lzm-S. In tissue-free experiments, we used a fluorometric assay (Ultra Amplex red H(2)O(2) assay) and electrochemical sensor techniques, respectively, to measure H(2)O(2) generation. We found that Lzm-S could generate H(2)O(2) and, furthermore, that this generation could be attenuated by the singlet oxygen quencher sodium azide. This study shows that Lzm-S, a mediator of sepsis, is able to intrinsically generate H(2)O(2). Moreover, this generation may activate H(2)O(2)-dependent pathways leading to cardiovascular collapse in septic shock.

Topics: Animals; Aspergillus niger; Cardiovascular Diseases; Catalase; Dogs; Enzyme Inhibitors; Hydrogen Peroxide; Muramidase; Myocardial Contraction; Nitric Oxide; Nitric Oxide Synthase Type III; omega-N-Methylarginine; Oxygen Consumption; Reactive Oxygen Species; Shock, Septic

Topics: Antibodies; Arteriosclerosis; Blood Vessels; Brain; Cardiovascular Diseases; Cerebrovascular Disorders; Endarteritis; Humans; Hypertension; Muramidase