Increased 12/15-Lipoxygenase Enhances Cell Growth, Fibronectin Deposition, and Neointimal Formation in Response to Carotid Injury

Deliri, Hamid; Meller, Nahum; Kadakkal, Ajay; Malhotra, Rohit; Brewster, Jordan A.; Doran, Amanda C.; Pei, Hong; Oldham, Stephanie; Skaflen, Marcus D.; Garmey, James C.; McNamara, Coleen A.

doi:10.1161/atvbaha.110.212068

Cited by 12 publications

(6 citation statements)

References 49 publications

(63 reference statements)

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“…In fact, bone marrow transplant studies in mice demonstrate that Id3 mediated atheroprotection is not all due to bone marrow derived cells [29]. 12/15-lipoxygenase, an important enzyme that modifies LDL in the sub-endothelial space of the atheroma, can upregulate Id3 expression in VSMCs and subsequently proliferation of VSMCs [30], [31]. Additionally, VCAM-1, an important adhesion molecule for leukocyte recruitment to the vessel wall, is upregulated in VSMCs and whole aortas isolated from Id3 −/− mice [12].…”

Section: Discussionmentioning

confidence: 99%

A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology

et al. 2014

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AimsWe previously identified association between the ID3 SNP rs11574 and carotid intima-media thickness in the Diabetes Heart Study, a predominantly White diabetic population. The nonsynonymous SNP rs11574 results in an amino acid substitution in the C-terminal region of ID3, attenuating the dominant negative function of ID3 as an inhibitor of basic HLH factor E12-mediated transcription. In the current investigation, we characterize the association between the functionally significant polymorphism in ID3, rs11574, with human coronary pathology.Methods and ResultsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal study of subclinical cardiovascular disease, including non-Hispanic White (n = 2,588), African American (n = 2,560) and Hispanic (n = 2,130) participants with data on coronary artery calcium (CAC). The Coronary Assessment in Virginia cohort (CAVA) included 71 patients aged 30–80 years, undergoing a medically necessary cardiac catheterization and intravascular ultrasound (IVUS) at the University of Virginia. ID3 SNP rs11574 risk allele was associated with the presence of CAC in MESA Whites (P = 0.017). In addition, the risk allele was associated with greater atheroma burden and stenosis in the CAVA cohort (P = 0.003, P = 0.04 respectively). The risk allele remained predictive of atheroma burden in multivariate analysis (Model 1: covariates age, gender, and LDL, regression coefficient = 9.578, SE = 3.657, p = 0.0110; Model 2: covariates Model 1, presence of hypertension, presence of diabetes, regression coefficient = 8.389, SE = 4.788, p = 0.0163).ConclusionsWe present additional cohorts that demonstrate association of ID3 SNP rs11574 directly with human coronary artery pathology as measured by CAC and IVUS: one a multiethnic, relatively healthy population with low levels of diabetes and the second a predominantly White population with a higher incidence of T2DM referred for cardiac catheterization.

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Section: Discussionmentioning

confidence: 99%

A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology

et al. 2014

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“…b , upper panel), and is also an important downstream molecule of the TGF‐β signaling pathway . In addition, Id3 has transcription corepressor activity, sequence‐specific DNA binding transcription factor activity, and it is reported to negatively regulate p21 expression, which is a potent cyclin‐dependent kinase inhibitor . Using qRT‐PCR, we further confirmed that all of the three members of the Id family ( Id1 , Id2 and Id3) were upregulated by S100A8 and S100A9 stimulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…b ). Recent research revealed that loss of Id3 enhances activation of the p21 promoter and abrogates cell proliferation . In this study, we noticed that both S100A8 and S100A9 stimulation decreased p21 mRNA expression levels (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Inflammation‐induced S100A8 activates Id3 and promotes colorectal tumorigenesis

Zhang

et al. 2015

Intl Journal of Cancer

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The aberrant expression of S100A8 and S100A9 is linked to nonresolving inflammation and ultimately to carcinogenesis, whereas the underlying mechanism that allows inflammation to progress to specific cancer types remains unknown. Here, we report that S100A8 was induced by inflammation and then promoted colorectal tumorigenesis downstream by activating Id3 (inhibitor of differentiation 3). Using gene expression profiling and immunohistochemistry, we found that both S100A8 and S100A9 were upregulated in the chemically-induced colitis-associated cancer mouse model and in human colorectal cancer specimens. Furthermore, we showed that S100A8 and S100A9 acted as chemoattractant proteins by recruiting macrophages, promoting the proliferation and invasion of colon cancer cell, as well as spurring the cycle that culminates in the acceleration of cancer metastasis in a nude mouse model. S100A8 regulated colon cancer cell cycle and proliferation by inducing Id3 expression while inhibiting p21. Id3 expression was regulated by Smad5, which was directly phosphorylated by Akt1. Our study revealed a novel mechanism in which inflammation-induced S100A8 promoted colorectal tumorigenesis by acting upstream to activate the Akt1-Smad5-Id3 axis.

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“…The major AA‐metabolizing enzymes cyclooxygenase 2, via production of prostaglandin E 2 acting on EP3 receptor,43 12/15 lipoxygenase, and CYP4A1/A2, most likely through generation of AA metabolites 12‐, 15‐, and 20‐hydroxyeicosatetraenoic acids, respectively, also contribute to neointimal growth 44, 45, 46, 47. Whether these enzymes and CYP1B1 act in a sequential or parallel and redundant manner is not known.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 1B1 Is Critical for Neointimal Growth in Wire‐Injured Carotid Artery of Male Mice

Mukherjee

Song

Estes

et al. 2018

JAHA

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BackgroundWe have reported that cytochrome P450 1B1 (CYP1B1), expressed in cardiovascular tissues, contributes to angiotensin II–induced vascular smooth muscle cell (VSMC) migration and proliferation and development of hypertension in various experimental animal models via generation of reactive oxygen species. This study was conducted to determine the contribution of CYP1B1 to platelet‐derived growth factor‐BB–induced VSMC migration and proliferation in vitro and to neointimal growth in vivo.Methods and Results VSMCs isolated from aortas of male Cyp1b1 +/+ and Cyp1b1 −/− mice were used for in vitro experiments. Moreover, carotid arteries of Cyp1b1 +/+ and Cyp1b1 −/− mice were injured with a metal wire to assess neointimal growth after 14 days. Platelet‐derived growth factor‐BB–induced migration and proliferation and H2O2 production were found to be attenuated in VSMCs from Cyp1b1 −/− mice and in VSMCs of Cyp1b1 +/+ mice treated with 4‐hydroxy‐2,2,6,6‐tetramethylpiperidin‐1‐oxyl, a superoxide dismutase and catalase mimetic. In addition, wire injury resulted in neointimal growth, as indicated by increased intimal area, intima/media ratio, and percentage area of restenosis, as well as elastin disorganization and adventitial collagen deposition in carotid arteries of Cyp1b1 +/+ mice, which were minimized in Cyp1b1 −/− mice. Wire injury also increased infiltration of inflammatory and immune cells, as indicated by expression of CD68+ macrophages and CD3+ T cells, respectively, in the injured arteries of Cyp1b1 +/+ mice, but not Cyp1b1 −/− mice. Administration of 4‐hydroxy‐2,2,6,6‐tetramethylpiperidin‐1‐oxyl attenuated neointimal growth in wire‐injured carotid arteries of Cyp1b1 +/+ mice.ConclusionsThese data suggest that CYP1B1‐dependent oxidative stress contributes to the neointimal growth caused by wire injury of carotid arteries of male mice.

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Increased 12/15-Lipoxygenase Enhances Cell Growth, Fibronectin Deposition, and Neointimal Formation in Response to Carotid Injury

Cited by 12 publications

References 49 publications

A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology

A Functionally Significant Polymorphism in ID3 Is Associated with Human Coronary Pathology

Inflammation‐induced S100A8 activates Id3 and promotes colorectal tumorigenesis

Cytochrome P450 1B1 Is Critical for Neointimal Growth in Wire‐Injured Carotid Artery of Male Mice

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