The relation between serum level of amioterminal propeptide of type I procollagen and diastolic dysfunction in hypertensive patients without diabetes mellitus: a pilot study

Lin, Yu Hung; Chiu, Yen‐Ling; Shiau, Yu‐Chien; Yen, Ruoh‐Fang; Tsai, I-Jung; Ho, Yi‐Lwun; Huang, Pei‐Hsin

doi:10.1038/sj.jhh.1002092

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…Procollagen type III N-terminal peptide, a serum marker for collagen synthesis (14) , increased progressively in saline-treated animals, but significantly decreased from baseline with GMCT treatment ( Figure 4A ). In addition, at 35d-PeAF, tissue levels of Gal-3 and TGF-β1 proteins in LA were significantly increased but Gal-1 was decreased; those effects were not affected by GMCT ( Figure 4B ).…”

Section: Resultsmentioning

confidence: 99%

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes

Takemoto

Ramírez

Yokokawa

et al. 2016

JACC: Basic to Translational Science

115

135

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Objectives To determine whether Gal-3 mediates sustained atrial fibrillation (AF)-induced atrial structural and electrical remodeling and contributes to AF perpetuation. Background Galectin-3 (Gal-3) mediates extracellular matrix remodeling in heart failure, but its role in AF progression remains unexplored. Methods We examined intracardiac blood samples from patients with AF (N=55) to identify potential biomarkers of AF recurrence. In a sheep model of tachypacing-induced AF (N=20), we tested the effects of Gal-3 inhibition during AF progression. Results In patients, intracardiac serum Gal-3 levels were greater in persistent than paroxysmal AF and independently predicted atrial tachyarrhythmia recurrences after a single ablation procedure. In the sheep model, both Gal-3 and TGF-β1 were elevated in the atria of persistent AF animals. The Gal-3 inhibitor GM-CT-01 (GMCT) reduced both Gal-3 and TGF-β1-induced sheep atrial fibroblast migration and proliferation in vitro. GMCT (12 mg/kg twice/week) prevented the increase in serum procollagen type III N-terminal peptide seen during progression to persistent AF, and also mitigated atrial dilatation, myocyte hypertrophy, fibrosis, and the expected increase in dominant frequency of excitation. Atria of GMCT-treated animals had significantly less TGF-β1-Smad2/3 signaling pathway activation and expression of α-smooth muscle actin and collagen than saline-treated animals. Ex-vivo hearts from GMCT-treated animals had significantly longer action potential durations and fewer rotors and wavebreaks during AF, and myocytes had lower functional expression of inward rectifier K+ channel (Kir2.3) than saline-treated animals. Importantly, GMCT increased the probability of spontaneous AF termination, decreased AF inducibility and reduced overall AF burden. Conclusions Inhibiting Gal-3 during AF progression might be useful as an adjuvant treatment to improve outcomes of catheter ablation for persistent AF. Gal-3 inhibition may be a potential new upstream therapy for prevention of AF progression.

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Section: Resultsmentioning

confidence: 99%

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes

Takemoto

Ramírez

Yokokawa

et al. 2016

JACC: Basic to Translational Science

115

135

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“…In a small cohort of 20 hypertensive patients without pHPT, higher P1NP was not associated with echocardiographic parameters of diastolic dysfunction [25]. High CTX was consistently associated with increased cardiovascular mortality in clinical studies [26–28].…”

Section: Discussionmentioning

confidence: 99%

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

et al. 2017

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Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the “Eplerenone in Primary Hyperparathyroidism” (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e’, diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e’ (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 0.198, P = 0.030) were each independently related with e’. CTX showed no correlations with LVEF or e’. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies.

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“…Using endomyocardial biopsies from hypertensive patients, a direct correlation was found between serum PICP and collagen volume fraction, while PICP levels were also higher in patients with severe fibrosis compared with those with less severe fibrosis [99]. Similarly, serum levels of PINP correlated with diastolic dysfunction in hypertensive patients without diabetes [100], suggesting that a serum marker of collagen synthesis (PICP or PINP) could be used as a biomarker for fibrosis in hypertensive patients. In hypertrophic cardiomyopathy, ECM turnover is a major determinant of cardiac remodeling.…”

Section: Reviewmentioning

confidence: 99%

Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease

Fan

Takawale

Lee

et al. 2012

Fibrogenesis Tissue Repair

685

540

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Fibroblasts comprise the largest cell population in the myocardium. In heart disease, the number of fibroblasts is increased either by replication of the resident myocardial fibroblasts, migration and transformation of circulating bone marrow cells, or by transformation of endothelial/epithelial cells into fibroblasts and myofibroblasts. The primary function of fibroblasts is to produce structural proteins that comprise the extracellular matrix (ECM). This can be a constructive process; however, hyperactivity of cardiac fibroblasts can result in excess production and deposition of ECM proteins in the myocardium, known as fibrosis, with adverse effects on cardiac structure and function. In addition to being the primary source of ECM proteins, fibroblasts produce a number of cytokines, peptides, and enzymes among which matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), directly impact the ECM turnover and homeostasis. Function of fibroblasts can also in turn be regulated by MMPs and TIMPs. In this review article, we will focus on the function of cardiac fibroblasts in the context of ECM formation, homeostasis and remodeling in the heart. We will discuss the origins and multiple roles of cardiac fibroblasts in myocardial remodeling in different types of heart disease in patients and in animal models. We will further provide an overview of what we have learned from experimental animal models and genetically modified mice with altered expression of ECM regulatory proteins, MMPs and TIMPs.

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The relation between serum level of amioterminal propeptide of type I procollagen and diastolic dysfunction in hypertensive patients without diabetes mellitus: a pilot study

Cited by 7 publications

References 10 publications

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes

Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease

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