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Record W1558476512 · doi:10.5772/21311

Role of Cathepsin K, L and S in Blood Vessel Remodeling

2011· book-chapter· en· W1558476512 on OpenAlexaff
O. Andriy, Dieter Brömme

Bibliographic record

VenueInTech eBooks · 2011
Typebook-chapter
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtease and Inhibitor Mechanisms
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsCathepsinInternal medicineChemistryMedicineBiochemistryEnzyme

Abstract

fetched live from OpenAlex

The development of cardiovascular diseases is characterized by the loss of structural integrity of blood vessels that requires extensive remodeling of the extra-cellular matrix (Michel et al., 2011; Garcia-Touchard et al., 2005). The entire aorta and some medium-sized arteries have elastic properties and mechanical strength allowing these vessels to withstand a surge of blood ejected from the heart. Such properties of blood vessels are contributed mostly by two major components of the extracellular matrix: elastin and collagen (Barbour et al., 2007; Wagenseil & Mecham, 2009; Sawabe, 2010). Elastin fibers are responsible for the elastic properties and collagen fibers provide mechanical strength to the arterial wall (Arteaga-Solis et al., 2000). These two proteins have a fibrillar structure and in their mature forms are very resistant to proteolysis. Thus elastin has a half-life around 50 years (Wagenseil & Mecham, 2009). However in some pathological conditions, excessive proteolytic activity results in extracellular matrix breakdown that is a key factor of arterial wall damage and the development of potential rupture. Sites of atherosclerotic and aneurysmatic lesions are characterized by increased elastoand collagenolytic activity (Diehm et al., 2007; Shimizu et al., 2006; Barbour et al., 2007; Sukhova et al., 1998). The dominant histological feature of aneurysmatic lesions is a chronic medial and adventitial inflammation resulting in medial degeneration and smooth muscle cell apoptosis. One of the most important contributors to aneurysmatic degeneration is an excessive loss of extracellular matrix. Fragmentation of elastin and collagen fibers is a characteristic feature of aneurysm formation and their loss is the ultimate cause of aneurysmatic rupture as well as rupture of atherosclerotic plaques (Shimizu et al., 2006; Sakalihasan et al., 2005; Diehm et al., 2007). Recently it has been shown that together with some matrix metalloproteinases, cathepsin K, L and S are the primary proteolytic culprits responsible for the breakdown of extracellular matrix proteins in blood vessels (Abdul-Hussien et al., 2010; Rizas et al., 2009; Sukhova & Shi, 2006). Cysteine proteinases cathepsin K, L and S belong to the most potent elastoand/or collagenolytic proteinases with potent abilities to degrade extracellular matrix. These enzymes attracted attention due to their upregulation within the aortic wall under different pathological conditions (Lutgens et al., 2007; Lafarge et al., 2010; Liu et al., 2004). Their expression was revealed in macrophages, smooth muscle cells and endothelial cells in atherosclerotic and aneurismal lesions in humans. These results instigated a series of studies on the involvement of cathepsin K, L and S in the development of cardiovascular diseases based on animal models of atherosclerosis and abdominal aortic aneurysm

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.814
Threshold uncertainty score0.812

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.213
Teacher spread0.199 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2011
Admission routes1
Has abstractyes

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