Plasma osteopontin levels in patients with dilated and hypertrophic cardiomyopathy

Podzimkova, Jana; Paleček, Tomáš; Kuchynka, Petr; Marek, Josef; Danek, Barbara Anna; Jáchymová, M; Kalousová, Marta; Zima, Tomáš; Linhart, Aleš

doi:10.1007/s00059-017-4645-3

Cited by 11 publications

(15 citation statements)

References 36 publications

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“…A study using coronary angiography showed that osteopontin levels were indeed associated with the presence and extent of coronary artery disease [ 38 ]. In line with our study, multiple studies also showed that elevated osteopontin may be a predictor of increased CVD risk in patients with diabetes [ 14 – 16 ], and osteopontin is elevated in heart failure patients [ 39 , 40 ]. Furthermore, osteopontin may also be involved in the coronary calcifications process by inhibiting hydroxyapatite formation [ 3 ].…”

Section: Discussionsupporting

confidence: 91%

Bone markers and cardiovascular risk in type 2 diabetes patients

Zwakenberg

Schouw

Schalkwijk

et al. 2018

Cardiovasc Diabetol

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BackgroundVascular calcifications are associated with a three- to fourfold increased risk of cardiovascular disease (CVD) and are highly prevalent in type 2 diabetes patients. Emerging evidence indicates that vascular calcification is a process of active bone formation regulated by stimulators and inhibitors of calcification. Therefore, this study aimed to evaluate whether six bone markers are associated with CVD risk in patients with type 2 diabetes.MethodsWe used data of a case-cohort study, nested in the EPIC-NL cohort, comprising 134 CVD cases and a random subcohort of 218 participants, all with type 2 diabetes at baseline. Six bone markers (osteocalcin, osteopontin, osteonectin, osteoprotegerin, alkaline phosphatase and sclerostin) were measured in baseline plasma samples with multiplex assays and information on CVD events was obtained. The association of bone makers with CVD risk was evaluated using Cox proportional hazard analyses.ResultsHigher concentrations of plasma osteopontin were associated (ptrend < 0.01) with an increased CVD risk with a hazard ratio of 2.00 (95%-CI 1.20–3.35) for the highest versus the lowest quartile in a multivariable adjusted model. The other bone markers were not associated with CVD risk.ConclusionsHigher osteopontin concentrations were associated with an increased CVD risk in type 2 diabetes patients. No consistent associations were found for the other five bone markers and risk of CVD in type 2 diabetes patients.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0691-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 91%

Bone markers and cardiovascular risk in type 2 diabetes patients

Zwakenberg

Schouw

Schalkwijk

et al. 2018

Cardiovasc Diabetol

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“…Cardiac hypertrophy is associated with increased expression of active NHE1 and OPN (10,43,44). However, a recent finding demonstrated that plasma OPN level is significantly increased in dilated cardiomyopathy subtype rather than hypertrophic cardiomyopathy, indicating that plasma OPN level is associated with overall heart failure severity (28). Our previous research had demonstrated that OPN is involved as a regulator in NHE1-induced cardiac hypertrophy in vitro (22,23).…”

Section: Discussionmentioning

confidence: 86%

Na⁺/H⁺exchanger isoform 1-induced osteopontin expression facilitates cardiac hypertrophy through p90 ribosomal S6 kinase

Abdulrahman

Jaspard-Vinassa

Fliegel

et al. 2018

Physiological Genomics

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Cardiovascular diseases are the leading cause of death worldwide. One in three cases of heart failure is due to dilated cardiomyopathy. The Na/H exchanger isoform 1 (NHE1), a multifunctional protein and the key pH regulator in the heart, has been demonstrated to be increased in this condition. We have previously demonstrated that elevated NHE1 activity induced cardiac hypertrophy in vivo. Furthermore, the overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an upregulation of myocardial osteopontin (OPN) expression. To determine the role of OPN in inducing NHE1-mediated cardiomyocyte hypertrophy, double transgenic mice expressing active NHE1 and OPN knockout were generated and assessed by echocardiography and the cardiac phenotype. Our studies showed that hearts expressing active NHE1 exhibited cardiac remodeling indicated by increased systolic and diastolic left ventricular internal diameter and increased ventricular volume. Moreover, these hearts demonstrated impaired function with decreased fractional shortening and ejection fraction. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA was upregulated, and there was an increase in heart cell cross-sectional area confirming the cardiac hypertrophic effect. Moreover, NHE1 transgenic mice also showed increased collagen deposition, upregulation of CD44 and phosphorylation of p90 ribosomal s6 kinase (RSK), effects that were regressed in OPN knockout mice. In conclusion, we developed an interesting comparative model of active NHE1 transgenic mouse lines which express a dilated hypertrophic phenotype expressing CD44 and phosphorylated RSK, effects which were regressed in absence of OPN.

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“…OPN also appears to play a role in several cardiomyopathies, including diabetic cardiomyopathy, in vivo [44,45] DCM both in mice [46] and in humans [7] and in patients with HCM [26]. The implication of OPN in idiopathic cardiomyopathies was also observed in hearts explanted at the time of cardiac transplantation, revealing an upregulation of OPN in cardiomyocytes [47].…”

Section: Role Of Opn In Heart Diseasementioning

confidence: 90%

“…The diverse biological functions of OPN can be attributable due to its structural features, PTMs, interaction with multiple receptors, and different isoforms [5,17]. Alternative translation of OPN generates two isoforms: A cell-secreted full length OPN (sOPN) and a shortened protein lacking the N-terminal signal sequence of sOPN, intracellular (iOPN), found in the cytoplasm and nucleus [26]. Studies investigating the involvement of OPN in cardiovascular diseases primarily focus on total OPN expression and do not take into account the expression levels of any specific OPN isoform [21].…”

Section: Osteopontin Structurementioning

confidence: 99%

“…OPN has emerged as a key ubiquitous phosphoprotein involved in numerous biological functions, including biomineralization, ECM and tissue remodeling and repair, immunity and the inflammatory response, cell death, and survival ( Figure 2) [24,26,28]. OPN's conformational flexibility mediates its interaction with a multitude of ligands across a dynamic array of cellular surfaces [27].…”

Section: Physiological Function Of Opnmentioning

confidence: 99%

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Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

Mohamed

Gadeau

Hasan

et al. 2019

Cells

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Osteopontin (OPN) is recognized for its significant roles in both physiological and pathological processes. Initially, OPN was recognized as a cytokine with pro-inflammatory actions. More recently, OPN has emerged as a matricellular protein of the extracellular matrix (ECM). OPN is also known to be a substrate for proteolytic cleavage by several proteases that form an integral part of the ECM. In the adult heart under physiological conditions, basal levels of OPN are expressed. Increased expression of OPN has been correlated with the progression of cardiac remodeling and fibrosis to heart failure and the severity of the condition. The intricate process by which OPN mediates its effects include the coordination of intracellular signals necessary for the differentiation of fibroblasts into myofibroblasts, promoting angiogenesis, wound healing, and tissue regeneration. In this review, we discuss the role of OPN in contributing to the development of cardiac fibrosis and its suitability as a therapeutic target.

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Plasma osteopontin levels in patients with dilated and hypertrophic cardiomyopathy

Abstract: Plasma OPN levels were associated with overall heart failure severity rather than with specific cardiomyopathy subtype in patients suffering from DCM or HCM, respectively.

Cited by 11 publications

References 36 publications

Bone markers and cardiovascular risk in type 2 diabetes patients

Bone markers and cardiovascular risk in type 2 diabetes patients

Na⁺/H⁺exchanger isoform 1-induced osteopontin expression facilitates cardiac hypertrophy through p90 ribosomal S6 kinase

Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

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Plasma osteopontin levels in patients with dilated and hypertrophic cardiomyopathy

Abstract: Plasma OPN levels were associated with overall heart failure severity rather than with specific cardiomyopathy subtype in patients suffering from DCM or HCM, respectively.

Cited by 11 publications

References 36 publications

Bone markers and cardiovascular risk in type 2 diabetes patients

Bone markers and cardiovascular risk in type 2 diabetes patients

Na+/H+exchanger isoform 1-induced osteopontin expression facilitates cardiac hypertrophy through p90 ribosomal S6 kinase

Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

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Na⁺/H⁺exchanger isoform 1-induced osteopontin expression facilitates cardiac hypertrophy through p90 ribosomal S6 kinase