2016
DOI: 10.1038/srep39553
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PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

Abstract: Raised endothelial shear stress is protective against atherosclerosis but such protection may be lost at sites of inflammation. We found that four splice variants of the peptidase inhibitor 16 (PI16) mRNA are among the most highly shear stress regulated transcripts in human coronary artery endothelial cells (HCAECs), in vitro but that expression is reduced by inflammatory mediators TNFα and IL-1β. Immunohistochemistry demonstrated that PI16 is expressed in human coronary endothelium and in a subset of neointim… Show more

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Cited by 57 publications
(52 citation statements)
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References 51 publications
(73 reference statements)
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“…We found that Mlinc.28428-positive cells under-expressed H19 and PI16 ( Figure 5A). These genes, that present a diversity of functions, are involved in stress mechanisms (oxydative response and shear stress), inflammation in fibroblasts and MSCs, and senescence pathways [81,82,83,84]. Despite the low number of differentially expressed genes in Mlinc.28428-positive cells, their functional behaviour and their known targets suggest a pathway linked to stress response and senescence establishment that reinforce our previous assumptions on Mlinc.28428 function.…”
Section: The Single Cell Rnaseq: An Emergent Level Of Completion In Msupporting
confidence: 70%
“…We found that Mlinc.28428-positive cells under-expressed H19 and PI16 ( Figure 5A). These genes, that present a diversity of functions, are involved in stress mechanisms (oxydative response and shear stress), inflammation in fibroblasts and MSCs, and senescence pathways [81,82,83,84]. Despite the low number of differentially expressed genes in Mlinc.28428-positive cells, their functional behaviour and their known targets suggest a pathway linked to stress response and senescence establishment that reinforce our previous assumptions on Mlinc.28428 function.…”
Section: The Single Cell Rnaseq: An Emergent Level Of Completion In Msupporting
confidence: 70%
“…If causal, this association could result from the profound influence of the haemodynamic environment in regulating endothelial function and dysfunction [25][26][27][28][29], with the response to elevated flow eliciting a distinct pattern of gene expression [17,37]. We and others have previously demonstrated that different flow patterns (and in our case pathologically-relevant elevated flow) changes endothelial behaviour and in particular the response to noxious stimuli that induce endothelial dysfunction [17,37,38]. In addition, the CFD simulations and subsequent statistical post-processing indicted that several OCT-defined erosions occurred in regions with modest or no stenosis, where the predominant flow feature was oscillatory shear stress (defined through OSI) [48,49].…”
Section: Discussionmentioning
confidence: 78%
“…Further studies should address the differential effects on cell death pathways of hyaluronan and HSP70 signalling through TLR2 and TLR4 under various flow conditions. In addition, the relative adhesive quality of a subendothelial matrix containing a higher proportion of hyaluronan and versican and possible contributions of extracellular matrix-degrading hydrolases requires elucidation, especially under elevated flow conditions [4,38,80]. These observations put a spotlight on the role of TLR2 and TLR4 and their ligands hyaluronan and HSP70, in modulating endothelial erosion in both haemodynamic environments.…”
Section: Discussionmentioning
confidence: 99%
“…Peptidase inhibitor 16 (PI16), which was lower in the LVA group, was assigned to this group. PI16 might contribute to electro-anatomical remodeling as the protein is known to be regulated by sheer stress, to inhibit ECM-remodeling matrix metalloproteinases, and is thought to maintain anti-inflammatory and non-activated cell homeostasis [27]. In context of heart failure, PI16 is supposed to inhibit myocyte hypertrophy [27].…”
Section: Fibrosis Inflammation and Electro-anatomical Remodelingmentioning
confidence: 99%