Circulating proteomic signature of early death in heart failure patients with reduced ejection fraction

Cuvelliez, Marie; Vandewalle, Vincent; Brunin, Maxime; Beseme, Olivia; Hulot, Audrey; Groote, P. De; Amouyel, Philippe; Bauters, Christophe; Marot, Guillemette; Pinet, Florence

doi:10.1038/s41598-019-55727-1

Cited by 24 publications

(24 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data suggest that MMP-7 may be an important mediator in the relationship between carotid stenosis and the development of recurrent cardiovascular events in different vascular territories. Nevertheless, the utility of MMP-7 as a potential biomarker may also be related to its role in other medical conditions, such as heart failure [36] as well as oncological diseases [37] .…”

Section: Discussionmentioning

confidence: 99%

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

Pérez‐Fernández

Irimia

Rodríguez

et al. 2020

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18 F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. Methods: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18 F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. Results: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18 F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18 F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18 F-FDG-PET was not significant. Conclusions: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

Pérez‐Fernández

Irimia

Rodríguez

et al. 2020

BMC Cardiovasc Disord

View full text Add to dashboard Cite

show abstract

“…Interestingly, MMP-7 recently showed its promising role as a novel biomarker, in patients with severe carotid stenosis, for recurrent cardiovascular events [153]. The elevated protein expression of MMP-1 and -7 was selected as potential candidates for early death prediction in patients with heart failure [154].…”

Section: Mps In Cardiovascular Diseasesmentioning

confidence: 99%

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

Raeeszadeh‐Sarmazdeh

Linh

Hritz

2020

Cells

199

155

View full text Add to dashboard Cite

The metalloproteinase (MP) family of zinc-dependent proteases, including matrix metalloproteinases (MMPs), a disintegrin and metalloproteases (ADAMs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) plays a crucial role in the extracellular matrix (ECM) remodeling and degradation activities. A wide range of substrates of the MP family includes ECM components, chemokines, cell receptors, and growth factors. Metalloproteinases activities are tightly regulated by proteolytic activation and inhibition via their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), and the imbalance of the activation and inhibition is responsible in progression or inhibition of several diseases, e.g., cancer, neurological disorders, and cardiovascular diseases. We provide an overview of the structure, function, and the multifaceted role of MMPs, ADAMs, and TIMPs in several diseases via their cellular functions such as proteolysis of other cell signaling factors, degradation and remodeling of the ECM, and other essential protease-independent interactions in the ECM. The significance of MP inhibitors targeting specific MMP or ADAMs with high selectivity is also discussed. Recent advances and techniques used in developing novel MP inhibitors and MP responsive drug delivery tools are also reviewed.

show abstract

“…It is also difficult to measure clinically and is interpreted via surrogate measures such as systemic vascular resistance via a pulmonary artery catheter. However, LV wall stress may not be the only contributor to the increased NT-proBNP, although higher levels of this peptide were found to correlate with mortality in patients with heart failure 45 .…”

Section: Discussionmentioning

confidence: 95%

Chronic cardiac structural damage, diastolic and systolic dysfunction following acute myocardial injury due to bromine exposure in rats

et al. 2020

View full text Add to dashboard Cite

Background: Highly reactive halogens such as bromine are more commonly utilized, leading to an increase in quantities that are stocked and transported, therefore increasing the risk of accidental or deliberate exposure. Here we describe progression and potential mechanisms of adverse effects of a single injurious insult on the heart caused by bromine inhalation. Our studies have shown that bromine inhalation causes acute myocardial ischemia-reperfusion-like injury mediated by cytosolic calcium overload and increased calpain activity due to inactivation of SERCA. However, the progression of this injury in survivors is unknown. Our working hypothesis is that the initial injury causes irreversible damage that leads to chronic left ventricular systolic and diastolic dysfunction.Methods: Sprague Dawley rats received bromine exposure of 600 ppm for 45' and the survivors were sacrificed at 14 or 28 days, with matching naïve groups at each time point. Echocardiography, hemodynamic analysis, histology, electron microscopy and biochemical analysis of cardiac tissue were performed to assess functional, structural and molecular effects.Results: At 14 and 28 days, hemodynamic and echocardiographic analysis revealed increases in RV and LV end-diastolic pressure and LV end-diastolic wall stress with increased LV fibrosis at 28 days. TEM images demonstrated myofibrillar loss, cytoskeletal breakdown and mitochondrial damage at both time points. The myofibrillar damage and increased LV wall stress was reflected by increases in cTnI and NT-proBNP at both time points. LV shortening decreased as a function of increasing LV end-systolic wall stress and was accompanied by increased SERCA modification and a striking dephosphorylation of phospholamban with a significant increase in protein phosphatase 1. There was an increased 4-hydroxynonenal content in the myocardium at 28 days suggesting increased oxidative stress. Conclusions:These results indicate that the initial insult of bromine inhalation initiates a continuous process with chronic myocardial damage and subsequent LV systolic and diastolic dysfunction and that oxidative stress and phospholamban dephosphorylation play a central role.

show abstract

Circulating proteomic signature of early death in heart failure patients with reduced ejection fraction

Cited by 24 publications

References 50 publications

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

Chronic cardiac structural damage, diastolic and systolic dysfunction following acute myocardial injury due to bromine exposure in rats

Contact Info

Product

Resources

About