scholarly journals Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients

2022 ◽  
Vol 8 ◽  
Author(s):  
Stephanie M. van der Voorn ◽  
Mimount Bourfiss ◽  
Anneline S. J. M. te Riele ◽  
Karim Taha ◽  
Marc A. Vos ◽  
...  
Keyword(s):  
Disease Severity ◽  
Collagen Type I ◽  
Tolerance Test ◽  
Clinical Disease ◽  
Type I ◽  
Premature Ventricular Contractions ◽  
Systolic Volume ◽  
Procollagen Type ◽  
Wave Inversion ◽  
Imaging Results

Background: Pathogenic variants in phospholamban (PLN, like p. Arg14del), are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN p.Arg14del carriers. During collagen synthesis and breakdown, propeptides are released into the circulation, such as procollagen type I carboxy-terminal propeptide (PICP) and C-terminal telopeptide collagen type I (ICTP).Aim: To investigate if PICP/ICTP levels in blood are correlative biomarkers for clinical disease severity and outcome in PLN p.Arg14del variant carriers.Methods: Serum and EDTA blood samples were collected from 72 PLN p.Arg14del carriers (age 50.5 years, 63% female) diagnosed with ACM (n = 12), DCM (n = 14), and preclinical variant carriers (n = 46). PICP levels were measured with an enzyme-linked immune sorbent assay and ICTP with a radio immuno-assay. Increased PICP/ICTP ratios suggest a higher collagen deposition. Clinical data including electrocardiographic, and imaging results were adjudicated from medical records.Results: No correlation between PICP/ICTP ratios and late gadolinium enhancement (LGE) was found. Moderate correlations were found between the PICP/ICTP ratio and end-diastolic/systolic volume (both rs = 0.40, n = 23, p = 0.06). PICP/ICTP ratio was significantly higher in patients with T wave inversion (TWI), especially in leads V4–V6, II, III, and aVF (p < 0.022) and in patients with premature ventricular contractions (PVCs) during an exercise tolerance test (p = 0.007).Conclusion: High PICP/ICTP ratios correlated with clinical parameters, such as TWI and PVCs. Given the limited size and heterogeneity of the patient group, additional studies are required to substantiate the incremental prognostic value of these fibrosis biomarkers in PLN p.Arg14del patients.

scholarly journals The effects of discontinuing long term alendronate therapy in a clinical practice setting

2011 ◽  
Vol 55 (4) ◽  
pp. 272-278 ◽  
Author(s):  
André Gonçalves da Silva ◽  
José Gilberto H. Vieira ◽  
Ilda Sizue Kunii ◽  
Janaína Martins de Lana ◽  
Marise Lazaretti-Castro
Keyword(s):  
Bone Turnover ◽  
Collagen Type I ◽  
Type I ◽  
Mineral Density ◽  
Procollagen Type ◽  
Post Menopausal Osteoporosis ◽  
Treatment Naïve ◽  
Turnover Markers ◽  
Group 2 ◽  
Post Menopausal

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7%) in G1 and one (5.2%) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

scholarly journals Immunoelectron microscopic localization of collagens type I, V, VI and of procollagen type III in human periodontal ligament and cementum.

1991 ◽  
Vol 39 (1) ◽  
pp. 103-110 ◽  
Author(s):  
J Becker ◽  
D Schuppan ◽  
J P Rabanus ◽  
R Rauch ◽  
U Niechoy ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Collagen Type ◽  
Ultrastructural Localization ◽  
Collagen Type I ◽  
Collagen Fibrils ◽  
Type I ◽  
Type Iii ◽  
Procollagen Type ◽  
Collagen Type Vi ◽  
Type V

We examined the ultrastructural localization of collagens Type I, V, VI and of procollagen Type III in decalcified and prefixed specimens of the periodontal ligament and cementum, by immunoelectron microscopy using ultra-thin cryostat sections. Immunostaining for collagen Type I was pronounced on the major cross-striated fibrils entering cementum and in cementum proper, whereas staining for procollagen Type III was almost exclusively observed on the major fibrils in the periodontal ligament situated more remote from cementum. Reactivity for collagen Type V was limited to aggregated, unbanded filamentous material of about 12 nm diameter that was found mainly in larger spaces between bundles of cross-striated collagen fibrils and occasionally on single microfibrils that apparently originated from the ends of the major collagen fibrils, which may support the concept of this collagen as a component of core fibrils. Collagen Type VI was present as microfilaments appearing to interconnect single cross-striated fibrils. In the densely packed fibril bundles of the periodontal ligament, no collagen type VI was detected. Neither Type V or Type VI collagen was observed in cementum.

scholarly journals Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

2018 ◽  
Vol 65 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Aleksandra Augusciak-Duma ◽  
Joanna Witecka ◽  
Aleksander L. Sieroń ◽  
Magdalena Janeczko ◽  
Jacek J Pietrzyk ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type ◽  
Collagen Type I ◽  
Base Substitution ◽  
Type I ◽  
Intracellular Accumulation ◽  
Single Base ◽  
Type Iii ◽  
Procollagen Type ◽  
Procollagen Type I

Over 85% of osteogenesis imperfecta (OI) cases associates to mutations in procollagen type I genes (COL1A1 or COL1A2), however, no hot spots were linked to particular clinical phenotypes. The 8 patients whom were clinically diagnosed with OI are from Polish population with no ethnic background indicated. Six unpublished mutations were detected in eight patients diagnosed with OI. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were also determined. In COL1A1 gene the mutations were found in exons 2, 22, 50 and in introns 13 and 51. In COL1A2 one mutation was identified in exon 22. Mutations of deletion type in COL1A1 that resulted in OI type I an effect neither on collagen type I secretion nor its intracellular accumulation were detected. Also, a single base substitution in I13 (c.904-9 G>T) was associated with OI type I. The OI type III was associated with single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly®Cys in the central part of triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation to procollagen type I. The results shall help in genetic counseling of OI patients and provide rational support in making by them and their families conscious, life important decisions.

scholarly journals Collagen Turnover Markers in Relation to Future Cardiovascular and Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

2017 ◽  
Vol 63 (7) ◽  
pp. 1237-1247 ◽  
Author(s):  
Daniel A Duprez ◽  
Myron D Gross ◽  
Otto A Sanchez ◽  
Jorge R Kizer ◽  
Joachim H Ix ◽  
...  
Keyword(s):  
Good Health ◽  
International Classification Of Diseases ◽  
Collagen Type I ◽  
Type I ◽  
Ethnic Study ◽  
Procollagen Type ◽  
Relative Risks ◽  
Total Death ◽  
Turnover Markers ◽  
Remodeling Of Extracellular Matrix

Abstract BACKGROUND Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and degradation. We studied their predictive value for future death and disease. METHODS A total of 3068 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory–related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n = 327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes. RESULTS Mean (SD) PIIINP was 5.47 (1.95) μg/L and ICTP was 3.37 (1.70) μg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (eGFR). Adjustment for age and eGFR attenuated relative risks, remaining 20%–30% per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model. CONCLUSIONS The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.

Cell-free collagen type I matrix for repair of cartilage defects—clinical and magnetic resonance imaging results

2011 ◽  
Vol 20 (10) ◽  
pp. 1915-1922 ◽  
Author(s):  
Turgay Efe ◽  
Christina Theisen ◽  
Susanne Fuchs-Winkelmann ◽  
Thomas Stein ◽  
Alan Getgood ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Collagen Type ◽  
Collagen Type I ◽  
Cartilage Defects ◽  
Type I ◽  
Resonance Imaging ◽  
Imaging Results

scholarly journals Fibrosis biomarkers as a predictive tool for clinical outcome in PLNR14Del patients

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
SM Van Der Voorn ◽  
M Bourfiss ◽  
ASJM Te Riele ◽  
K Taha ◽  
MA Vos ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Clinical Data ◽  
Collagen Type ◽  
Collagen Type I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Blood Collection ◽  
Type I ◽  
T Wave ◽  
Wave Inversion

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Netherlands Cardio Vascular Research Initiative (CVON): the Dutch heart foundation Background Mutations in phospholamban (PLN, most often PLNR14Del), a protein that regulates Ca2+ homeostasis in cardiomyocytes, are found in patients diagnosed with arrhythmogenic (ACM) and dilated cardiomyopathy (DCM). Fibrosis formation in the heart is one of the hallmarks in PLN patients, which compromises cardiac contractility and predisposes to arrhythmogenicity. Collagen type I is the most abundant type of collagen in the heart (85%). During continuous collagen synthesis propeptides, like procollagen type I carboxy-terminal propeptide (PICP) and during collagen breakdown, C-terminal telopeptide collagen type I (ICTP), are released into the circulation. Clinically, detection of fibrosis occurs via echo or MRI, however difficulties arise when patchy fibrosis has to be detected. Purpose To investigate if PICP and ICTP levels in blood are useful predictive biomarkers for clinical outcome in PLN patients. Methods 78 serum and EDTA blood samples were collected on the same day from ACM diagnosed (n = 12), DCM diagnosed (n = 14) or non-classified (n = 52) PLN patients. PICP levels were measured with an ELISA assay and ICTP with a RIA. Clinical data were subtracted two years around blood collection from Redcap, a Dutch database with medical records from PLN patients. Data were not normally distributed, so Spearman’s correlation coefficient and Mann-Whitney test were used. Results Gender, age and PICP/ICTP ratios were similarly distributed between the subgroups. First, we checked if clinical data subtracted two years around blood collection provided reliable results regarding clinical outcome. Patients who underwent clinical testing  5.5 weeks around blood collection revealed that clinical data were in line with the best-fitted line of the linear regression and therefore provide reliable results. Next, the potential correlation of fibrosis biomarkers with electrical parameters was assessed. Increased PICP/ICTP ratios suggest a higher collagen deposition. Although there was no correlation with prolonged QRS duration (Rs 0.13, n = 62, ns), subgroup analysis showed a significant weak correlation for non-classified patients (Rs 0.32, n = 38, p = 0.05). No significant correlation was found for ACM or DCM patients; however, groups were rather small. PICP/ICTP ratio was significantly higher in patients with T wave inversion and premature ventricular contractions (PVCs) during an exercise tolerance test. A weak inverted correlation was found with left ventricular ejection fraction and PICP/ICTP (Rs -0.28, n = 23, ns), while moderate correlations between the ratio and end diastolic volume, and end systolic volume exist (both Rs 0.40, n = 23, p = 0.06). Conclusion High PICP/ICTP ratios correlate with clinical outcome in PLN patients, such as T wave inversion and PVCs. However, the size and heterogeneity of the patient group resulted in weak to moderate correlation coefficients and might therefore currently precludes to use PICP and ICTP levels as biomarker.

Abstract 2799: Procollagen Type III Amino-terminal and Carboxyl-terminal Telopeptide of Collagen type I but not Carboxyl-terminal Propeptide Type I are Associated with Heart Failure in the Elderly; The Cardiovascular Health Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Eddy Barasch ◽  
John S. Gottdiener ◽  
Gerard Aurigemma ◽  
DW Kitzman ◽  
Jing Han ◽  
...  
Keyword(s):  
Cardiovascular Health ◽  
Collagen Type ◽  
Roc Curves ◽  
The Elderly ◽  
Collagen Type I ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Type I ◽  
Procollagen Type ◽  
Carboxyl Terminal

Background: The presence of excess myocardial matrix fibrosis (MF) contributes to alteration in the left ventricular (LV) diastolic and eventually, systolic performance. The increased collagen-derived serum peptides associated with collagen synthesis (procollagen type III aminoterminal peptide-PIIINP-, carboxyl-terminal propeptide type I -PIP-) and degradation (carboxyl-terminal telopeptide of collagen type I -CTIP-) have been shown in a number of small studies to correlate with histologic assessment of MF. While the prevalence of heart failure (HF), especially diastolic (D)HF increases with aging, no large studies evaluate the association of MF with DHF or systolic (S) HF in the elderly. Aims: To determine the association between the 3 biomarkers of MF turnover Methods: In 880 participants (ppt), mean age 77 ± 6 yrs, 52 % males, 79 % white, enrolled in the Cardiovascular Health Study, a prospective community based study of individuals > 65 yrs of age , serum levels of PIIINP, PIP and ICTP were measured by radioimmunoassay; 179 had HF with normal LVEF (DHF), 131 had HF with LVEF ± 55%, (SHF), 287 controls (no HF) and 283 healthy ppts. Results: Logistic regression models using a progressive number of adjustment variables are illustrated in the table . The ROC curves showed for CTIP the AUC =0.69; p<0.0001 and for PIIINP, AUC = 0.66, p<0.0001. The comparison of two ROC curves = NS. Model 1: unadjusted model Model 2: adjusted by age, gender and race Model 3: model 2+ adjustment for LVH, hypertension, diabetes, CHD, any ACE inhibitor, potassium-sparing agents alone, any diuretic, serum creatinine, cystatin C Conclusions: 1. PIP was not associated with SHF or DHF. 2. Even when adjusted for multiple potential confounders, there is still a strong association between CTIP, PIIINP and DHF as well as SHF. 3. The lack of association between PIP and HF might be a characteristic of this age group where possible PIIINP, reflecting the poorly cross-linked collagen, predominates .

Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone

2005 ◽  
Vol 288 (6) ◽  
pp. E1222-E1228 ◽  
Author(s):  
Tomoyuki Iwasaki ◽  
Koji Mukasa ◽  
Masato Yoneda ◽  
Satoshi Ito ◽  
Yoshihiko Yamada ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Protein Accumulation ◽  
Transcriptional Level ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I

Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10−6 M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.

scholarly journals The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis

2011 ◽  
Vol 164 (4) ◽  
pp. 643-648 ◽  
Author(s):  
Maria Luchavova ◽  
Vit Zikan ◽  
Dana Michalska ◽  
Ivan Raska ◽  
Ales A Kubena ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Bone Turnover ◽  
Collagen Type I ◽  
Time Of Day ◽  
Repeated Measurements ◽  
Type I ◽  
Procollagen Type ◽  
Teriparatide Treatment ◽  
Procollagen Type I ◽  
Turnover Markers

BackgroundWe hypothesized that with the administration of teriparatide (TPTD) treatment at different times, we would be able to modify the physiological circadian rhythm of bone turnover.MethodsThe concentration of serum C-terminal telopeptide of collagen type I (βCTX), serum N-terminal propeptide of procollagen type I (P1NP), serum ionized calcium (iCa), and plasma PTH were measured every 3 h over a 24 h period in 14 postmenopausal osteoporotic women (aged 72.4±9.3 years) treated with 20 μg TPTD for long term, given at different times of the day. General linear model-repeated measurements (GLM RM) were performed to analyze the circadian rhythms as well as intergroup comparisons.ResultsGLM-RM for both related groups showed a significant influence of time of day on all measured variables except P1NP. The analysis for each group separately provided a powerful model for βCTX (P<0.001, η2=0.496), serum iCa (P<0.001, η2=0.423), plasma PTH (P<0.001, η2=0.283), and serum PINP (P<0.001, η2=0.248). While the evening TPTD treatment showed a marked circadian rhythm for serum βCTX, the morning TPTD treatment rather suggested circasemidian rhythm. The P1NP rhythm followed a much smaller amplitude of the rhythm than βCTX. Changes in serum iCa were positively related to changes in serum βCTX (P<0.001) and negatively related to changes in PTH (P<0.001).ConclusionTiming of TPTD administration may significantly change the 24 h variation in bone turnover markers as well as calcium-parathyroid axis in postmenopausal osteoporotic women.

scholarly journals Pheophorbide a Derivatives Exert Antiwrinkle Effects on UVB-Induced Skin Aging in Human Fibroblasts

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 147
Author(s):  
Hwa Lee ◽  
Ho-Yong Park ◽  
Tae-Sook Jeong
Keyword(s):  
Mrna Expression ◽  
Human Fibroblasts ◽  
Collagen Type I ◽  
Skin Aging ◽  
Breakdown Product ◽  
Type I ◽  
Pheophorbide A ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Pyropheophorbide A

Pheophorbide a is a chlorophyll metabolic breakdown product. This study investigated the antiwrinkle effect of pheophorbide a (PA) and its derivatives, including pyropheophorbide a (PyroPA) and pyropheophorbide a methyl ester (PyroPA-ME), on ultraviolet (UV) B-stimulated CCD-986sk fibroblasts. PA, PyroPA, and PyroPA-ME effectively suppressed reactive oxygen species accumulation in UVB-exposed CCD-986sk fibroblasts. All three pheophorbides also reduced UVB-induced matrix metalloproteinase (MMP)-1 secretion and mRNA expression of MMP-1, MMP-2, and MMP-9. Treatment with pheophorbides resulted in increased procollagen synthesis, and this required enhancement of procollagen type I C-peptide content and mRNA expression of collagen type I alpha 1 (COL1A1) and COL1A2 in CCD-986sk cells. These antiwrinkle effects were more potent with PA and PyroPA than with PyroPA-ME. Furthermore, PA and PyroPA suppressed UVB-induced phosphorylation of extracellular signal-regulated protein kinase and c-Jun N-terminal kinase but not p38. Moreover, all three pheophorbides inhibited NF-κB p65 phosphorylation. Therefore, these pheophorbides, especially PA and PyroPA, can be used as antiwrinkle agents, and PA- or PyroPA-rich natural resources can be used in functional cosmetics.

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