Detection of Cardiac Allograft Rejection and Response to Immunosuppressive Therapy With Peripheral Blood Gene Expression

Horwitz, Phillip A.; Tsai, Emily J.; Putt, Mary; Gilmore, Joan; Lepore, John J.; Parmacek, Michael S.; Kao, Andrew; Desai, Shashank; Goldberg, Lee R.; Brozena, Susan C.; Jessup, Mariell; Epstein, Jonathan A.; Cappola, Thomas P.

doi:10.1161/01.cir.0000150539.72783.bf

Cited by 146 publications

(90 citation statements)

References 26 publications

(20 reference statements)

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“…Molecular mechanisms underlying several human diseases have been investigated by gene expression analysis of peripheral blood mononuclear cells (PBMC) as surrogates for predicting potential effects in tissues that are not easily accessible (Eady et al, 2005). These cells have been proposed as a useful tool to better understand multiple sclerosis related pathways (Achiron and Gurevich, 2006), the pathophysiology of Alzheimer's disease (Maes et al, 2006), hepatic diseases (Chiappini et al, 2006;Patalay et al, 2005), oncology (DePrimo et al, 2003;Twine et al, 2003), and cardiovascular research (Horwitz et al, 2004). Also, peripheral blood mononuclear cells (PBMC) were suggested as a surrogate tissue to muscle biopsies to study mitochondrial dysfunction (Abu-Amero and Bosley, 2005;Marriage et al, 2003).…”

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confidence: 99%

Differential Expression of Oxidative Stress and Inflammation Related Genes in Peripheral Blood Mononuclear Cells in Response to a Low-Calorie Diet: A Nutrigenomics Study

Crujeiras

Parra

Milagro

et al. 2008

OMICS: A Journal of Integrative Biology

102

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Nutrigenomics is a new application of omics technologies in nutritional science. Nutrigenomics aims to identify molecular markers of diet-related diseases and mechanisms of interindividual variability in response to food. The aim of this study was to evaluate peripheral blood mononuclear cells (PBMC) as a model system and readily available source of RNA to discern gene expression signatures in relation to personalized therapy of obesity. PBMC were collected from obese men before and after an 8-week low-calorie diet (LCD) to lose weight. Changes in gene expression before and after the LCD were initially screened using a DNA-microarray platform and validated by qRT-PCR. Global gene expression analysis identified 385 differentially expressed transcripts after the LCD. Further analyses showed a decrease in some specific oxidative stress and inflammation genes. Interestingly, expression of these genes was directly related to body weight, while a lower IL8 gene expression was associated with higher fat mass decrease. Collectively, these observations suggest that PBMCs are a suitable RNA source and model system to perform nutrigenomics studies related to obesity and development of personalized dietary treatments. IL8 gene expression warrant further research as a putative novel biomarker of changes in body fat percentage in response to an LCD. 251

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mentioning

confidence: 99%

Differential Expression of Oxidative Stress and Inflammation Related Genes in Peripheral Blood Mononuclear Cells in Response to a Low-Calorie Diet: A Nutrigenomics Study

Crujeiras

Parra

Milagro

et al. 2008

OMICS: A Journal of Integrative Biology

102

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“…In fact, even the CD14+ monocytes are composed of different sub-populations that when further fractionated, may improve gene expression sensitivity and provide new insights. Finally, by combining genomic information from other studies examining plaque macrophages or peripheral mononuclear cells in distinct immunologic processes such as cardiac allograft rejection (Horwitz et al 2004), we may uncover unique information that will assist us in genetically dissecting the complexities of human atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Circulating Cells: A Window Into Atherosclerosis

Kang

Patino

Matoba

et al. 2006

Trends in Cardiovascular Medicine

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Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. Diagnostic markers of inflammation and atherosclerosisBased on our current understanding of atherosclerosis, the pathogenesis of this leading cause of morbidity and mortality in westernized societies is best described by chronic vascular inflammation that starts early in life and exacerbates with aging (Glass and Witztum 2001, Hansson 2005). Multiple hereditary and environmental factors contribute to the initiation and progression of this disease (Lusis 2000). However, some well established clinical risk factors such as low density lipoprotein (LDL) and the metabolic syndrome (including obesity and insulin-resistance, diabetes) and basic factors such as angiotensin II all appear to promote oxidative stress and inflammation (Daugherty and Cassis 2004, Glass and Witztum 2001, Libby 2002. Though a number of molecules linked to inflammation have been proposed for use as atherosclerosis markers, C-reactive protein (CRP) has gained prominence because of its association with increased cardiovascular risk in clinical trials (Jain and Ridker 2005). Revealing insights into statins' mechanism of action, the recent clinical trial PROVE IT-TIMI 22 separated the cholesterol lowering and anti-inflammatory effects of statin therapy by demonstrating the independent and additive predictive values of serum cholesterol and CRP levels on cardiovascular events, respectively (Jain andRidker 2005, Ridker et al. 2005). A question that follows such fundamental observations is whether there exist other predictive markers that have equal or greater sensitivity and specificity. Th...

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“…As reviewed elsewhere (Hershberger review in this journal issue), genetic information is already being used clinically for single gene disorders such as channelopathies [23,24] and Familial Hypercholesterolemia [25,26]. There is also a growing number of clinical genetic tests for nonMendelian settings such as breast cancer [27,28] and cardiac transplantation [29,30]. These clinical genetic tests are being used in two different ways-generating detailed disease characterization or establishing disease susceptibility.…”

Section: Clinical Implications Of Genetic Informationmentioning

confidence: 99%

Cardiovascular Genetic Medicine: The Genetics of Coronary Heart Disease

Seo

Goldschmidt‐Clermont

2008

J. of Cardiovasc. Trans. Res.

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Advances in genomic technologies have provided researchers with an unprecedented opportunity to identify genes that may contribute to the development of coronary heart disease. The power of these technologies lies in their ability to survey the entire genome in a nonbiased fashion to find genes and gene variants associated with coronary heart disease. This article reviews different genomic approaches for studying coronary heart disease and the clinical implications of using genetic information.

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Detection of Cardiac Allograft Rejection and Response to Immunosuppressive Therapy With Peripheral Blood Gene Expression

Cited by 146 publications

References 26 publications

Differential Expression of Oxidative Stress and Inflammation Related Genes in Peripheral Blood Mononuclear Cells in Response to a Low-Calorie Diet: A Nutrigenomics Study

Differential Expression of Oxidative Stress and Inflammation Related Genes in Peripheral Blood Mononuclear Cells in Response to a Low-Calorie Diet: A Nutrigenomics Study

Genomic Analysis of Circulating Cells: A Window Into Atherosclerosis

Cardiovascular Genetic Medicine: The Genetics of Coronary Heart Disease

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