Neutrophil serine proteases and their endogenous inhibitors in coronary artery ectasia patients

Liu, Ruifeng; Chen, Lianfeng; Wu, Wei; Chen, Houzao; Zhang, Shuyang

doi:10.5152/akd.2015.6072

Cited by 10 publications

(11 citation statements)

References 29 publications

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“…Indeed, cardiac disease has been described in MPS III patients as well as in patients affected by the other MPS subtypes [178,179]. Multiple evidence demonstrated the involvement of CTSs in many cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, myocardial infarction, and hypertension, some of which are common clinical manifestations in MPSs [8,10,[17][18][19]36,56,61,66,76,80,81]. In particular, CTSB results in being up-regulated in cardiomyocytes in response to hypertrophic stimuli both in vivo and in vitro [180].…”

Section: Cathepsin Involvement In the Pathophysiology Of Mucopolysaccmentioning

confidence: 99%

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

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Section: Cathepsin Involvement In the Pathophysiology Of Mucopolysaccmentioning

confidence: 99%

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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“…Previous studies have revealed a potential contribution of trappin‐2 to the pathological process of vascular disorders. For instance, serum trappin‐2 levels are elevated in patients with coronary artery ectasia, and trappin‐2 deposition is abundantly seen in the involved vascular walls of neutrophil‐mediated cutaneous vasculitis . Since SSc is featured by vascular injury and/or vascular activation followed by extensive organ fibrosis, our initial hypothesis was the up‐regulated expression of trappin‐2 in SSc vasculature.…”

Section: Discussionmentioning

confidence: 99%

A potential contribution of trappin‐2 to the development of vasculopathy in systemic sclerosis

Miyagawa

Asano

Saigusa

et al. 2019

Acad Dermatol Venereol

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Background Trappin-2/pre-elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodelling, which consist of the complex pathological process of systemic sclerosis (SSc).Objectives To clarify the potential role of trappin-2 in SSc.Methods Serum trappin-2 levels were determined by enzyme-linked immunosorbent assay in 51 SSc and 18 healthy subjects. Trappin-2 expression was evaluated in SSc lesional skin and cultured endothelial cells treated with FLI1 siRNA by immunohistochemistry, reverse transcription-real-time PCR and/or immunoblotting. Friend leukaemia virus integration 1 (Fli1) binding to the PI3 promoter was assessed by chromatin immunoprecipitation.Results Since serum trappin-2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction, SSc patients with normal renal function were analysed. Although serum trappin-2 levels were comparable between diffuse cutaneous SSc, limited cutaneous SSc and control subjects, the prevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin-2 levels than in those with normal levels. Furthermore, serum trappin-2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without. Moreover, serum trappin-2 levels positively correlated with RVSP values in SSc patients. Importantly, trappin-2 expression was enhanced in small vessels of SSc lesional skin.In cultured endothelial cells, trappin-2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels and Fli1 occupied the PI3 promoter.Conclusions Endothelial trappin-2 up-regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy.

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“…It was reported that peripheral neutrophil counts and neutrophil-lymphocyte ratios were significantly higher in coronary ectasia patients [ 24 , 25 ]. Inappropriate activation of neutrophils leads to increased levels of neutrophil elastase and neutrophil serine proteases, which increase the degradation of elastin fibres and the transition of collagen from type III to type I in coronary vascular walls [ 26 , 27 ]. At the same time, significant endothelial dysfunction and high oxidative stress were also documented in patients with CAE [ 20 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation of increased corrected TIMI frame counts and the topographical extent of isolated coronary artery ectasia

Zhang

Guo

et al. 2018

BMC Cardiovasc Disord

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BackgroundThe precise relationship between increased thrombolysis in myocardial infarction (TIMI) frame counts and the topographical extent of isolated coronary artery ectasia (CAE) has not been fully explained. New parameters of linear dimension (LD) and the estimated ectatic area (EEA) together with the diameter and ectasia ratio may be associated with the corrected TIMI frame count (CTFC) in isolated CAE patients.MethodsThe topographical parameters of ectatic coronary arteries and/or segments of 77 isolated CAE patients were consecutively studied. The CTFC for each coronary artery was determined by angiographic frame count.ResultsRight coronary artery (RCA) was the most frequently affected. The RCA and left circumflex (LCX) had significantly longer LD (p < 0.001 for both), and greater EEA (p < 0.001 for both) than those of left anterior descending artery (LAD). Similarly, the RCA and LCX have higher CTFCs (p = 0.001 and p = 0.008, respectively) than LAD. All topographic parameters and CTFCs were positively correlated with Markis classification. Linear regression analyses revealed that CTFCs were strongly correlated with diameter, LD, ectasia ratio and EEA, while EEA was the best predictor for the CTFC. Among multiple linear and nonlinear regression models, the cubic model between the CTFC and EEA exhibits the best Goodness-of-Fit.ConclusionThe severity of the topographical extent of CAE was significantly correlated with increased CTFCs. Both the linear dimension and ectatic diameter (combined as EEA) were important for evaluating decreased coronary flow in isolated CAE patients.Electronic supplementary materialThe online version of this article (10.1186/s12872-018-0833-1) contains supplementary material, which is available to authorized users.

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Neutrophil serine proteases and their endogenous inhibitors in coronary artery ectasia patients

Cited by 10 publications

References 29 publications

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

A potential contribution of trappin‐2 to the development of vasculopathy in systemic sclerosis

Correlation of increased corrected TIMI frame counts and the topographical extent of isolated coronary artery ectasia

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