Examining Variation and Temporal Dynamics of Extracellular Matrix Biomarkers Following Acute Myocardial Infarction

Brunton-O’Sullivan, Morgane M.; Holley, A.; Bird, Georgina K; Kristono, Gisela A; Harding, Scott; Larsen, Peter

doi:10.2217/bmm-2021-0531

Cited by 5 publications

(6 citation statements)

References 30 publications

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“…Indeed, concentrations of syndecan-4 [27] and osteopontin [28] are reported to peak between Day 1 and 3 after MI, although later peaks are also reported for syndecan-4 [20]. Contrary to the other biomarkers, periostin levels increased during the initial four months, which can be explained by an early suppression post-MI as observed in other studies [29,30], with a later increase related to tissue remodelling. The time-dependent variation in the biomarker concentrations stress the need for standardized sampling time points and multiple measurements.…”

Section: Plos Onementioning

confidence: 56%

Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality

Andrup,

Andersen,

Hoffmann

et al. 2024

PLoS ONE

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Background We aimed to determine whether serum levels of proteins related to changes in cardiac extracellular matrix (ECM) were associated with ischemic injury assessed by cardiac magnetic resonance (CMR) and mortality in patients with ST-elevation myocardial infarction (STEMI). Methods The concentrations of six ECM-related proteins (periostin, osteopontin, syndecan-1, syndecan-4, bone morphogenetic protein 7, and growth differentiation factor (GDF)-15) were measured in serum samples from patients on Day 1 and Month 4 after STEMI (n = 239). Ischemic injury was assessed by myocardial salvage index, microvascular obstruction, infarct size, and left ventricular function measured by CMR conducted during the initial admission (median 2 days after admission) and after 4 months. All-cause mortality was recorded after a median follow-up time of 70 months. Results Levels of periostin increased from Day 1 to Month 4 after hospitalization, while the levels of GDF-15, osteopontin, syndecan-1, and syndecan-4 declined. At both time points, high levels of syndecan-1 were associated with microvascular obstruction, large infarct size, and reduced left ventricular ejection fraction, whereas high levels of syndecan-4 at Month 4 were associated with a higher myocardial salvage index and less dilatation of the left ventricle. Higher mortality rates were associated with periostin levels at both time points, low syndecan-4 levels at Month 4, or high GDF-15 levels at Month 4. Conclusions In patients with STEMI, we found an association between serum levels of ECM biomarkers and ischemic injury and mortality. The results provide new insight into the role ECM components play in ischemic injury following STEMI and suggests a potential for these biomarkers in prognostication after STEMI.

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Section: Plos Onementioning

confidence: 56%

Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality

Andrup,

Andersen,

Hoffmann

et al. 2024

PLoS ONE

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“…Accumulating evidence indicate that MMP proteins, including MMP3 (also known as stromelysin-1), are closely associated with MI and heart failure [36][37][38][39]. Thus they can be used as biomarkers and potential therapeutic targets for cardiovascular diseases [40][41][42]. Moreover, polymorphisms of the MMP3 gene are correlated with the genetic risk of MI, suggesting a possible contribution of this gene to the occurrence of this condition [43,44].…”

Section: Discussionmentioning

confidence: 99%

IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification

Zhang¹,

Shen

et al. 2023

Preprint

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Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction. IGF2BP3 expression progressively decreases during postnatal development and becomes undetectable in the adult heart. However, it is strongly upregulated after cardiac injury. Both gain- and loss-of-function analyses indicate that IGF2BP3 regulates cardiomyocyte proliferation in vitro and in vivo. In particular, IGF2BP3 promotes cardiac regeneration and improves cardiac function after myocardial infarction. Mechanistically, we demonstrate that IGF2BP3 binds to and stabilizes MMP3 mRNA through interaction with N6-methyladenosine modification. The expression of MMP3 protein is also progressively downregulated during postnatal development. Functional analyses indicate that MMP3 acts downstream of IGF2BP3 to regulate cardiomyocyte proliferation. These results suggest that IGF2BP3-mediated post-transcriptional regulation of extracellular matrix and tissue remodeling contributes to cardiomyocyte regeneration. They should help to define therapeutic strategy for ameliorating myocardial infarction by inducing cell proliferation and heart repair.

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“…For example, PINP is a biomarker of collagen type I synthesis that is not specific to myocardial tissue alone. However, we have selected an optimal panel of ECM biomarkers based on previous testing that suggested these biomarkers were altered in AMI patients compared to healthy volunteers [ 19 ]. This study comprises a moderate sample size and is explorative in nature.…”

Section: Discussionmentioning

confidence: 99%

“…The biomarker panel selected for this study comprised the following: MMP-2, MMP-3, MMP-8, MMP-9, periostin, PINP and TIMP-1. In a previous study, we demonstrated that these ECM biomarkers were of interest to investigate in a prognostic setting following AMI [ 19 ]. Specifically, we showed that levels of these biomarkers were significantly altered in AMI patients when compared to healthy volunteers and that these biomarkers were stably expressed in the first 3 days following symptom onset, confirming opportunistic blood sampling during acute hospital admission.…”

Section: Methodsmentioning

confidence: 99%

“…The aim of this study was to assess if combining ECM biomarkers using EFA or cluster analysis could more accurately predict the development of impaired systolic function in AMI patients when compared to single biomarker analysis. Seven ECM biomarkers were examined in this study based on previously published findings that suggest MMP-2, MMP-3, MMP-8, MMP-9, periostin, PINP and TIMP-1 were an optimal biomarker panel to assess prognostic outcomes in AMI [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Cluster analysis of extracellular matrix biomarkers predicts the development of impaired systolic function within 1 year of acute myocardial infarction

et al. 2022

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The clinical utility of combining extracellular matrix (ECM) biomarkers to predict the development of impaired systolic function following acute myocardial infarction (AMI) remains largely undetermined. A combination of ELISA and multiplexing assays were performed to measure matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, MMP-9, periostin, N-terminal type I procollagen (PINP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma samples from 120 AMI patients. All patients had an echocardiogram within 1 year of AMI, and were divided into impaired (n = 37, LVEF < 50%) and preserved (n = 83, LVEF ≥ 50%) systolic function groups. Exploratory factor analysis was performed on log-transformed biomarkers using principle axis analysis with Oblimin rotation. Cluster analysis was performed on log-transformed and normalised biomarkers using Ward’s method of minimum variance and the squared Euclidean distance metric. Upon univariate analysis, current smoking, prescription of ACE inhibitors at discharge, peak hsTnT > 610 ng/L (median), MMP-8 levels, Factor 1 scores and Cluster One assignment were predictive of impaired systolic function. Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04–7.23], p = 0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables. These observations support the usefulness of combining ECM biomarkers using cluster analysis for predicting the development of impaired systolic function in AMI patients.

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Examining Variation and Temporal Dynamics of Extracellular Matrix Biomarkers Following Acute Myocardial Infarction

Cited by 5 publications

References 30 publications

Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality

Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality

IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification

Cluster analysis of extracellular matrix biomarkers predicts the development of impaired systolic function within 1 year of acute myocardial infarction

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