Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in Vascular Remodeling of Stented Coronary Arteries

Suna, Gonca; Wojakowski, Wojciech; Lynch, Magnus; Barallobre-Barreiro, Javier; Yin, Xiaoke; Mayr, Ursula; Baig, Ferheen; Lu, Ruifang; Fava, Marika; Hayward, Robert; Molenaar, Chris; White, Stephen J.; Roleder, Tomasz; Milewski, Krzysztof; Gąsior, Paweł; Buszman, Piotr P.; Buszman, Paweł; Jahangiri, Marjan; Shanahan, Catherine M.; Hill, Jonathan; Mayr, Manuel

doi:10.1161/circulationaha.116.023381

Cited by 91 publications

(77 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated that the VSMCs play a fundamental role in the pathogenesis of vascular lesions, including lipid retention, ECM production, and plaque integrity maintenance [33,34]. Previous studies have reported that ADAMTS-5 and proteoglycans were expressed in human coronary arterial VSMCs [16]. Consistent with previous reports, doubleimmunofluorescence staining indicated that the VSMCs were the major source of ADAMTS-5 in human CAD atherosclerotic plaques.…”

Section: Variablessupporting

confidence: 83%

“…ADAMTS-5, known as aggrecanase-2, has the highest aggrecanase activity and contributes to vascular remodeling [16,17]. Suna et al reported that the expression level of ADAMTS-5 was markedly decreased in stent-induced vascular injury, associated with the accumulation of proteoglycans, notably aggrecan and versican [16]. In addition, decreased ADAMTS-5 expression was found in atherosclerosis of apolipoprotein E (ApoE) null mice, associated with the accumulation of aggrecan and versican [18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ADAMTS-5 Decreases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease

Wang

et al. 2019

Disease Markers

View full text Add to dashboard Cite

The current study demonstrates that a disintegrin and metalloproteinase with thrombospondin type 1 motif- (ADAMTS-) 5 is a key extracellular matrix protease and associated with cardiovascular diseases. However, the plasma ADAMTS-5 levels and relevance of coronary artery disease (CAD) remain largely unknown. This study is aimed at examining the relationship between the plasma ADAMTS-5 levels and the severity of coronary stenosis in patients with CAD. In the present study, the expression of ADAMTS-5 was analyzed in coronary artery samples and blood. The results showed that the plasma ADAMTS-5 levels were lower in the CAD group than in the control group. In addition, significantly higher matrix metalloproteinase- (MMP-) 2 and MMP-9 levels were also observed in the patients with CAD, and the ADAMTS-5 levels were negatively correlated with the MMP-2 and MMP-9 levels. Spearman’s correlation analysis showed that the Gensini score was negatively correlated with the ADAMTS-5 levels but was positively correlated with the MMP-2 and MMP-9 levels. Receiver-operating characteristic (ROC) analysis revealed that ADAMTS-5, MMP-2, and MMP-9 may have a certain diagnostic value in CAD and that the combination of all three metalloproteinases had a higher diagnostic value. The findings provided a better understanding of the role of ADAMTS-5 in the diagnosis of CAD.

show abstract

Section: Variablessupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

ADAMTS-5 Decreases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease

Wang

et al. 2019

Disease Markers

View full text Add to dashboard Cite

show abstract

“…As indicated above, TLRs play a crucial role in the early inflammatory triggers that initiate vein graft remodeling. Among the first mediators of inflammation in vein grafts are DAMPs such as aggrecan and heat shock proteins ( 135 , 136 ). Endogenous DAMPs activate TLRs that are expressed by cells in the vein graft wall such as endothelial cells and SMCs ( 1 , 73 , 137 ).…”

Section: Immune Modulationmentioning

confidence: 99%

Inflammation in Vein Graft Disease

Vries

Quax

2018

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Bypass surgery is one of the most frequently used strategies to revascularize tissues downstream occlusive atherosclerotic lesions. For venous bypass surgery the great saphenous vein is the most commonly used vessel. Unfortunately, graft efficacy is low due to the development of vascular inflammation, intimal hyperplasia and accelerated atherosclerosis. Moreover, failure of grafts leads to significant adverse outcomes and even mortality. The last couple of decades not much has changed in the treatment of vein graft disease (VGD). However, insight is the cellular and molecular mechanisms of VGD has increased. In this review, we discuss the latest insights on VGD and the role of inflammation in this. We discuss vein graft pathophysiology including hemodynamic changes, the role of vessel wall constitutions and vascular remodeling. We show that profound systemic and local inflammatory responses, including inflammation of the perivascular fat, involve both the innate and adaptive immune system.

show abstract

“…With proteins executing the majority of cellular structural and functional roles 14 , proteome analytics obviates misinterpretation due to discrepancies between transcript and protein readouts arising from posttranscriptional processing and splicing, and differing mRNA versus corresponding protein isoform half-lives. Indeed, use of proteomicsbased assessment has proven increasingly valuable for comprehending cardiovascular biology in health and disease [15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome

et al. 2020

View full text Add to dashboard Cite

Cardiopoietic stem cells have reached advanced clinical testing for ischemic heart failure. To profile their molecular influence on recipient hearts, systems proteomics was here applied in a chronic model of infarction randomized with and without human cardiopoietic stem cell treatment. Multidimensional label-free tandem mass spectrometry resolved and quantified 3987 proteins constituting the cardiac proteome. Infarction altered 450 proteins, reduced to 283 by stem cell treatment. Notably, cell therapy nonstochastically reversed a majority of infarction-provoked changes, remediating 85% of disease-affected protein clusters. Pathway and network analysis decoded functional reorganization, distinguished by prioritization of vasculogenesis, cardiac development, organ regeneration, and differentiation. Subproteome restoration nullified adverse ischemic effects, validated by echo-/electrocardiographic documentation of improved cardiac chamber size, reduced QT prolongation and augmented ejection fraction postcell therapy. Collectively, cardiopoietic stem cell intervention transitioned infarcted hearts from a cardiomyopathic trajectory towards pre-disease. Systems proteomics thus offers utility to delineate and interpret complex molecular regenerative outcomes.

show abstract

Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in Vascular Remodeling of Stented Coronary Arteries

Abstract: Supplemental Digital Content is available in the text.

Cited by 91 publications

References 49 publications

ADAMTS-5 Decreases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease

ADAMTS-5 Decreases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease

Inflammation in Vein Graft Disease

Cardiopoietic stem cell therapy restores infarction-altered cardiac proteome

Contact Info

Product

Resources

About