-
JAMA Cardiology May 2017Accumulating evidence links inflammation and atrial fibrillation (AF).
IMPORTANCE
Accumulating evidence links inflammation and atrial fibrillation (AF).
OBJECTIVE
To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population.
DESIGN, SETTING, AND PARTICIPANTS
The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909). The population included a random sample of the general community aged 40 to 79 years. Levels of 13 inflammation markers were measured at baseline in 1990. Findings were replicated in a case-control sample nested within the prospective Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1770). Data analysis was performed from February to May 2016.
EXPOSURES
Levels of 13 inflammation markers.
MAIN OUTCOMES AND MEASURES
Incident AF over a 20-year follow-up period in the Bruneck Study.
RESULTS
Of the 909 participants included in the Bruneck Study, mean [SD] age was 58.8 (11.4) years and 448 (49.3%) were women. Among the 880 participants free of prevalent AF (n = 29) at baseline, 117 developed AF during the 20-year follow-up period (incidence rate, 8.2; 95% CI, 6.8-9.6 per 1000 person-years). The levels of soluble vascular cell adhesion molecule 1 (VCAM-1) and osteoprotegerin were significantly associated with incident AF (hazard ratio [HR], 1.49; 95% CI, 1.26-1.78; and 1.46; 95% CI, 1.25-1.69, respectively; P < .001 with Bonferroni correction for both), but osteoprotegerin lost significance after age and sex adjustment (HR, 1.05; 95% CI, 0.87-1.27; P > .99 with Bonferroni correction). Matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of nuclear factor-κB ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance (after Bonferroni correction in unadjusted and age- and sex-adjusted analyses). The HR for a 1-SD higher soluble VCAM-1 level was 1.34 (95% CI, 1.11-1.62; Bonferroni-corrected P = .03) in a multivariable model. The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide (multivariable HR for a 1-SD higher N-terminal pro-B-type natriuretic peptide level, 1.15; 95% CI, 1.04-1.26), internally consistent in various subgroups, and successfully replicated in the SAPHIR Study (age- and sex-adjusted, and multivariable odds ratios for a 1-SD higher soluble VCAM-1 level, 1.91; 95% CI, 1.24-2.96, P = .003; and 2.59; 95% CI, 1.45-4.60; P = .001).
CONCLUSIONS AND RELEVANCE
Levels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset AF in the general community. Future studies should address whether soluble VCAM-1 is capable of improving AF risk classification beyond the information provided by standard risk scores.
Topics: Adult; Aged; Atrial Fibrillation; Austria; Biomarkers; Cohort Studies; Female; Humans; Incidence; Inflammation; Italy; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Proportional Hazards Models; Prospective Studies; Reproducibility of Results; Stroke; Vascular Cell Adhesion Molecule-1
PubMed: 28355442
DOI: 10.1001/jamacardio.2017.0064 -
Biomedicines Apr 2024Osteopontin (OPN) and osteoprotegerin (OPG) are glycoproteins that participate in the regulation of tissue biomineralization. The aim of the project is to verify the...
Osteopontin (OPN) and osteoprotegerin (OPG) are glycoproteins that participate in the regulation of tissue biomineralization. The aim of the project is to verify the hypothesis that the content of OPN and OPG in the aorta walls increases with the development of atherosclerosis and that these proteins are quantitatively related to the main proteins in the extracellular arteries matrix. Quantitative and qualitative analyses of the OPN and OPG content in 101 aorta sections have been conducted. Additionally, an enzyme-linked immunosorbent assay (ELISA) test has been performed to determine the collagen types I-IV and elastin content in the tissues. Correlations between the biochemical data and patients' age/sex, atherosclerosis stages, and calcification occurrences in the tissue have been established. We are the first to report correlations between OPN or OPG and various types of collagen and elastin content (OPG/type I collagen correlation: r = 0.37, = 0.004; OPG/type II collagen: r = 0.34, = 0.007; OPG/type III collagen: r = 0.39, = 0.002, OPG/type IV collagen: r = 0.27, = 0.03; OPG/elastin: r = 0.42, = 0.001; OPN/collagen type I: r = 0.34, = 0.007; OPN/collagen type II: r = 0.52, = 0.000; OPN/elastin: r = 0.61, = 0.001). OPN overexpression accompanies calcium deposit (CA) formation with the protein localized in the calcium deposit, whereas OPG is located outside the CA. Although OPN and OPG seem to play a similar function (inhibiting calcification), these glycoproteins have different tissue localizations and independent expression regulation. The independent expression regulation presumably depends on the factors responsible for stimulating the synthesis of collagens and elastin.
PubMed: 38672202
DOI: 10.3390/biomedicines12040847 -
Journal of Clinical Medicine Jun 2022Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance of normal estrogen and androgen levels in the blood. Androgens play an...
Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance of normal estrogen and androgen levels in the blood. Androgens play an important role in the female body because they influence bone mineral density (BMD), body mass composition, muscle mass, mental state, and the regulation of sexual function. The reduced activity of aromatase, due to mutations in the gene, reduces the estrogen pool in favor of androgens. Clinically, aromatase deficiency causes hyperandrogenism in women. Therefore, the aim of the study was to assess the effect of the gene polymorphism on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group was comprised of 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, total sRANKL (free and bound RANKL), osteoprotegerin, and total 25-OH Vitamin D. An analysis of the gene polymorphisms was performed using the real-time PCR method. The GG genotype of the rs700518 polymorphism turned out to be associated with: FEI (Free Estradiol Index), SHGB concentration, estradiol concentration, and insulin concentration determined in the glucose tolerance test 60' compared to AG and AA genotypes. Patients with the AG genotype had a higher ratio of android to gynoid fat and a greater content of visceral adipose tissue. Higher visceral tissue content may reduce BMD. In conclusion, the study showed that the rs700518 polymorphism may be associated with the distribution of adipose tissue in young women with hyperandrogenism. These results suggest that patients with the AG genotype may develop osteoporosis.
PubMed: 35743606
DOI: 10.3390/jcm11123537 -
PloS One 2016Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of...
BACKGROUND
Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls.
METHODS
Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.
RESULTS
We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.
CONCLUSIONS
Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority of these markers do not differ markedly by disease status.
Topics: Adult; Aged; Biomarkers; Blood Glucose; Carbohydrate Metabolism; Case-Control Studies; Female; Ghrelin; Human Growth Hormone; Humans; Huntington Disease; Hydrocortisone; Insulin; Leptin; Lipid Metabolism; Male; Middle Aged
PubMed: 26744893
DOI: 10.1371/journal.pone.0146480 -
Journal of Personalized Medicine Jun 2021This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary...
This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.
PubMed: 34205079
DOI: 10.3390/jpm11060506 -
Computational Intelligence and... 2022The target of the present paper was to reveal the influence of LncRNA BC083743 on osteogenesis in human bone marrow mesenchymal stem cells (hBMSCs).
OBJECTIVE
The target of the present paper was to reveal the influence of LncRNA BC083743 on osteogenesis in human bone marrow mesenchymal stem cells (hBMSCs).
METHODS
Serum specimens from osteoporotic patients and normal subjects were collected to isolate hBMSCs from femoral head tissue. The levels of BC083743 and miR-103-3p in serum and hBMSCs were measured by QRT-PCR. Alkaline phosphatase (ALP) activity test and alizarin red dyeing were used to identify ALP activity and mineralization forming ability of hBMSCs after transfection with si-BC083743 (siRNA-targeting BC083743). In addition, QRT-PCR and immunoblotting were conducted to identify the expressing levels of Runt-related transcription factor 2(Runx2), osteoprotegerin (OPG), and bone morphogenetic protein 2 (BMP2) in hBMSCs. Dual-luciferase reporter gene and RNA pull-down assays were employed to substantiate the binding of BC083743 to miR-103-3p and miR-103-3p to SATB2.
RESULTS
BC083743 expression was significantly downregulated in sera from patients with osteoporosis, and osteogenic differentiation-related genes and BC083743 expression were obviously upregulated as the time to osteogenic differentiation increased. BC083743 knockdown hindered the osteogenic differentiation of hBMSCs. BC083743 was aimed at miR-103-3p and miR-103-3p inhibitors partially reversed the inhibitory effect of BC083743 downregulation on hBMSCs osteogenesis. BC083743 silencing downregulated SATB2 through uptake of miR-103-3p, thereby inhibiting hBMSCs osteogenesis to exacerbate osteoporosis.
CONCLUSION
BC083743/miR-103-3p/SATB2 axis inhibited osteogenic differentiation and exacerbated osteoporosis, which may offer brand-new molecular aims for the treatment of clinical osteoporosis.
Topics: Cells, Cultured; Humans; Matrix Attachment Region Binding Proteins; MicroRNAs; Osteogenesis; Osteoporosis; RNA, Long Noncoding; Transcription Factors
PubMed: 35769281
DOI: 10.1155/2022/7066759 -
Clinical Journal of the American... Jan 2014IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients. (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Serum IGF-1 and other biochemical, clinical (subjective global assessment), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status and mineral and bone metabolism were measured in a cohort of 365 Swedish clinically stable CKD stage 5 patients (median age of 53 years) initiating dialysis between 1994 and 2009; in 207 patients, measurements were also taken after 1 year of dialysis. Deaths were registered during a median follow-up of 5 years. Associations of mortality with baseline IGF-1 and changes of IGF-1 after 1 year of dialysis were evaluated by Cox models.
RESULTS
At baseline, IGF-1 concentrations associated negatively with age, diabetes mellitus, cardiovascular disease, poor nutritional status, IL-6, and osteoprotegerin and positively with body fat mass, bone mineral density, serum phosphate, calcium, and fibroblast growth factor-23. At 1 year, IGF-1 had increased by 33%. In multivariate regression, low age, diabetes mellitus, and high serum phosphate and calcium associated with IGF-1 at baseline, and in a mixed model, these factors, together with high fat body mass, associated with changes of IGF-1 during the first 1 year of dialysis. Adjusting for calendar year of inclusion, age, sex, diabetes mellitus, cardiovascular disease, IL-6, and poor nutritional status, a 1 SD higher level of IGF-1 at baseline associated with lower mortality risk (hazard ratio, 0.57; 95% confidence interval, 0.32 to 0.98). Persistently low or decreasing IGF-1 levels during the first 1 year on dialysis predicted worse survival (adjusted hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.50).
CONCLUSION
In incident dialysis patients, low serum IGF-1 associates with body composition and markers of mineral and bone metabolism, and it predicts increased mortality risk.
Topics: Adult; Aged; Biomarkers; Body Composition; Bone Remodeling; Chi-Square Distribution; Cross-Sectional Studies; Down-Regulation; Female; Humans; Insulin-Like Growth Factor I; Kaplan-Meier Estimate; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Nutritional Status; Proportional Hazards Models; Renal Dialysis; Risk Factors; Sweden; Time Factors; Treatment Outcome
PubMed: 24178975
DOI: 10.2215/CJN.02470213 -
BMJ Open Jun 2023Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and bone turnover markers.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
METHODS
Searches were carried out in PubMed, EMBASE, Web of science, Cochrane library, ClinicalTrials.gov from database inception to 26 September 2022. Two review authors assessed trial eligibility in accordance with established inclusion criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB V.2.0). Data analysis was conducted with Stata Statistical Software V.16.0 and Review Manager Software V.5.3.
RESULTS
A total of 15 studies with 3394 participants were identified for the present meta-analysis. Our pooled results indicated that metformin had no statistically significant effects on BMD at lumbar spine (SMD=-0.05, 95% CI=0.19 to 0.09, p=0.47, participants=810; studies=7), at femoral (MD=-0.01 g/cm, 95% CI=-0.04 to 0.01 g/cm, p=0.25, participants=601; studies=3) and at hip (MD=0.01 g/cm, 95% CI=0.02 to 0.03 g/cm, p=0.56, participants=634; studies=4). Metformin did not lead to significant change in osteocalcin, osteoprotegerin and bone alkaline phosphatase. Metformin induced decreases in N-terminal propeptide of type I procollagen (MD=-6.09 µg/L, 95% CI=9.38 to -2.81 µg/L, p=0.0003, participants=2316; studies=7) and C-terminal telopeptide of type I collagen (MD=-55.80 ng/L, 95% CI=97.33 to -14.26 ng/L, p=0.008, participants=2325; studies=7).
CONCLUSION
This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the outcomes should be interpreted with caution due to several limitations.
Topics: Humans; Bone Density; Metformin; Lumbar Vertebrae; Bone Remodeling
PubMed: 37355276
DOI: 10.1136/bmjopen-2023-072904 -
Brazilian Dental Journal 2017The aim of this study was to evaluate osteoclastogenesis signaling in midpalatal suture after rapid maxillary expansion (RME) in rats. Thirty male Wistar rats were...
The aim of this study was to evaluate osteoclastogenesis signaling in midpalatal suture after rapid maxillary expansion (RME) in rats. Thirty male Wistar rats were randomly assigned to two groups with 15 animals each: control (C) and RME group. RME was performed by inserting a 1.5-mm-thick circular metal ring between the maxillary incisors. The animals were euthanized at 3, 7 and 10 days after RME. qRT-PCR was used to evaluate expression of Tnfsf11 (RANKL), Tnfrsf11a (RANK) and Tnfrsf11b (OPG). Data were submitted to statistical analysis using two-way ANOVA followed by Tukey test (a=0.05). There was an upregulation of RANK and RANKL genes at 7 and 10 days and an upregulation of the OPG gene at 3 and 7 days of healing. Interestingly, an increased in expression of all genes was observed over time in both RME and C groups. The RANKL/OPG ratio showed an increased signaling favoring bone resorption on RME compared to C at 3 and 7 days. Signaling against bone resorption was observed, as well as an upregulation of OPG gene expression in RME group, compared to C group at 10 days. The results of this study concluded that the RANK, RANK-L and OPG system participates in bone remodeling after RME.
Topics: Animals; Bone Remodeling; Gene Expression; Male; Maxilla; Osteogenesis; Osteoprotegerin; Palatal Expansion Technique; RANK Ligand; Rats, Wistar; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction; Up-Regulation; Wound Healing
PubMed: 29297549
DOI: 10.1590/0103-6440201601116 -
Diabetes Care Sep 2022To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death. (Clinical Trial)
Clinical Trial
OBJECTIVE
To use protein biomarkers to identify people with type 2 diabetes at high risk of cardiovascular outcomes and death.
RESEARCH DESIGN AND METHODS
Biobanked serum from 4,957 ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial participants was analyzed. Forward-selection Cox models identified independent protein risk factors for major adverse cardiovascular events (MACE) and death that were compared with a previously validated biomarker panel.
RESULTS
NT-proBNP and osteoprotegerin predicted both outcomes. In addition, trefoil factor 3 predicted MACE, and angiopoietin-2 predicted death (C = 0.70 and 0.79, respectively, compared with 0.63 and 0.66 for clinical variables alone). These proteins had all previously been identified and validated. Notably, C statistics for just NT-proBNP plus clinical risk factors were 0.69 and 0.78 for MACE and death, respectively.
CONCLUSIONS
NT-proBNP and other proteins independently predict cardiovascular outcomes in people with type 2 diabetes following acute coronary syndrome. Adding other biomarkers only marginally increased NT-proBNP's prognostic value.
Topics: Acute Coronary Syndrome; Biomarkers; Diabetes Mellitus, Type 2; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors
PubMed: 35817031
DOI: 10.2337/dc22-0453