Circulating CD31+ leukocyte frequency is associated with cardiovascular risk factors

Ge, Yin; Cheng, Susan; Larson, Martin G.; Ghorbani, Anahita; Grande, Rafael; Klein, Rachael J.; O’Donnell, Christopher J.; Vasan, Ramachandran S.; Shaw, Stanley Y.; Wang, Thomas J.; Cohen, Kenneth S.

doi:10.1016/j.atherosclerosis.2013.04.017

Cited by 11 publications

(11 citation statements)

References 32 publications

(35 reference statements)

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“…Moreover, we have detected CD31 in other cell types likewise, especially in cancer‐derived leukocytes it was identified quite abundantly as well (data not shown). CD31 + leukocytes have also been observed by others, for example, in patients with cardiovascular diseases . The finally obtained signature correctly classified endothelial cells isolated from the liver, bone marrow, lung, and ovaries, all at normal and inflammatory activated cell states (data not shown).…”

Section: Resultssupporting

confidence: 57%

Determination of cell type‐specific proteome signatures of primary human leukocytes, endothelial cells, keratinocytes, hepatocytes, fibroblasts and melanocytes by comparative proteome profiling

et al. 2014

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Cells gain their functional specialization by different protein synthesis. A lot of knowledge with respect to cell type-specific proteins has been collected during the last thirty years. This knowledge was built mainly by using antibodies. Nowadays, modern MS, which supports comprehensive proteome analyses of biological samples, may render possible the search for cell type-specific proteins as well. However, a therefore necessary systematic MS study comprising many different cell types has not been performed until now. Here we present a proteome analysis strategy supporting the automated and meaningful comparison of any biological samples. We have presently applied this strategy to six different primary human cell types, namely leukocytes, endothelial cells, keratinocytes, hepatocytes, fibroblasts, and melanocytes. Comparative analysis of the resulting proteome profiles allowed us to select proteins specifically identified in one of the six cell types and not in any of the five others. Based on these results, we designated cell type-specific proteome signatures consisting each of six such characteristic proteins. These signatures independently reproduced well-known marker proteins already established for FACS analyses in addition to novel candidate marker proteins. We applied these signatures for the interpretation of proteome profiles obtained from the analyses of hepatocellular carcinoma-associated tissue homogenates and normal liver tissue homogenates. The identification of members of the above described signatures gave us an indication of the presence of characteristic cells in the diseased tissues and thus supported the interpretation of the proteomics data of these complex biological samples.

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Section: Resultssupporting

confidence: 57%

Determination of cell type‐specific proteome signatures of primary human leukocytes, endothelial cells, keratinocytes, hepatocytes, fibroblasts and melanocytes by comparative proteome profiling

et al. 2014

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“…We found that smoking was associated with a decrease in BM CD45 + CD31 + lymphocytes. Similar to our findings, Ge et al [14] found a negative association between smoking and the level of circulating CD45 +− CD31 dim lymphocytes in healthy men and women. Further investigation of this cell type is warranted to determine its role in the prevention or repair of cardiac injury.…”

Section: Discussionsupporting

confidence: 92%

“…In our study, increased age was inversely associated with the frequency of CD45 + CD31 + lymphocytes. This is similar to the findings of, both Hur et al [19] and Ge et al [14] who showed an inverse correlation between the level of circulating peripheral blood CD31 + T cells and age. One possible explanation for this decrease in cell number with age is age-related apoptosis.…”

Section: Discussionsupporting

confidence: 92%

“…These CRFs have been shown to correlate with changes in the frequencies of particular cell types in the blood. Recently, it was reported that hypertension is associated with an increase in the level of circulating CD11b + cells [38], advanced age and smoking are associated with a decrease in circulating CD31 + leukocytes [14], age is inversely associated with the level of CD34 + cells [30], and diabetes is associated with a decrease in circulating endothelial progenitor cells [26]. …”

Section: Introductionmentioning

confidence: 99%

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Identification of cardiovascular risk factors associated with bone marrow cell subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME and LateTIME clinical trials

Contreras¹,

Orozco²,

Resende³

et al. 2016

Basic Res Cardiol

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Autologous bone marrow mononuclear cell (BM-MNC) therapy for patients with ST-segment elevation myocardial infarction (STEMI) has produced inconsistent results, possibly due to BM-MNC product heterogeneity. Patient-specific cardiovascular risk factors (CRFs) may contribute to variations in BM-MNC composition. We sought to identify associations between BM-MNC subset frequencies and specific CRFs in STEMI patients. Bone marrow was collected from 191 STEMI patients enrolled in the CCTRN TIME and LateTIME trials. Relationships between BM-MNC subsets and CRFs were determined with multivariate analyses. An assessment of CRFs showed that hyperlipidemia and hypertension were associated with a higher frequency of CD11b+ cells (P = 0.045 and P = 0.016, respectively). In addition, we found that females had lower frequencies of CD11b+ (P = 0.018) and CD45+CD14+ (P = 0.028) cells than males, age was inversely associated with the frequency of CD45+CD31+ cells (P = 0.001), smoking was associated with a decreased frequency of CD45+CD31+ cells (P = 0.013), glucose level was positively associated with the frequency of CD45+CD3+ cells, and creatinine level (an indicator of renal function) was inversely associated with the frequency of CD45+CD3+ cells (P = 0.015). In conclusion, the frequencies of monocytic, lymphocytic, and angiogenic BM-MNCs varied in relation to patients’ CRFs. These phenotypic variations may affect cell therapy outcomes and might be an important consideration when selecting patients for and reviewing results from autologous cell therapy trials.

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“…We focused our study on CD31 − DP-MSCs to exclude cells that may express some of these markers although being not MSCs. Indeed, some endothelial cells are known to express CD146 and Stro-1, and natural killer cells and some lymphocytes may express CD56 (Shi and Gronthos, 2003; Woodfin et al, 2007; Crisan et al, 2008; Ge et al, 2013; Lv et al, 2014; Harkness et al, 2016; Melsen et al, 2016). Flow cytometry was recently used to characterize the various populations of immune cells present in the human DP with a strategy of progressive cell gating (Gaudin et al, 2015), and we designed in the present study a similar strategy to allow for the identification and quantification of DP-MSC subpopulations.…”

Section: Discussionmentioning

confidence: 99%

Immunophenotyping Reveals the Diversity of Human Dental Pulp Mesenchymal Stromal Cells In vivo and Their Evolution upon In vitro Amplification

Ducret

Fabre

Degoul³

et al. 2016

Front. Physiol.

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Mesenchymal stromal/stem cells (MSCs) from human dental pulp (DP) can be expanded in vitro for cell-based and regenerative dentistry therapeutic purposes. However, their heterogeneity may be a hurdle to the achievement of reproducible and predictable therapeutic outcomes. To get a better knowledge about this heterogeneity, we designed a flow cytometric strategy to analyze the phenotype of DP cells in vivo and upon in vitro expansion with stem cell markers. We focused on the CD31− cell population to exclude endothelial and leukocytic cells. Results showed that the in vivo CD31− DP cell population contained 1.4% of CD56+, 1.5% of CD146+, 2.4% of CD271+ and 6.3% of MSCA-1+ cells but very few Stro-1+ cells (≤ 1%). CD56+, CD146+, CD271+, and MSCA-1+ cell subpopulations expressed various levels of these markers. CD146+MSCA-1+, CD271+MSCA-1+, and CD146+CD271+ cells were the most abundant DP-MSC populations. Analysis of DP-MSCs expanded in vitro with a medicinal manufacturing approach showed that CD146 was expressed by about 50% of CD56+, CD271+, MSCA-1+, and Stro-1+ cells, and MSCA-1 by 15–30% of CD56+, CD146+, CD271+, and Stro-1+ cells. These ratios remained stable with passages. CD271 and Stro-1 were expressed by <1% of the expanded cell populations. Interestingly, the percentage of CD56+ cells strongly increased from P1 (25%) to P4 (80%) both in all sub-populations studied. CD146+CD56+, MSCA-1+CD56+, and CD146+MSCA-1+ cells were the most abundant DP-MSCs at the end of P4. These results established that DP-MSCs constitute a heterogeneous mixture of cells in pulp tissue in vivo and in culture, and that their phenotype is modified upon in vitro expansion. Further studies are needed to determine whether co-expression of specific MSC markers confers DP cells specific properties that could be used for the regeneration of human tissues, including the dental pulp, with standardized cell-based medicinal products.

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Circulating CD31+ leukocyte frequency is associated with cardiovascular risk factors

Cited by 11 publications

References 32 publications

Determination of cell type‐specific proteome signatures of primary human leukocytes, endothelial cells, keratinocytes, hepatocytes, fibroblasts and melanocytes by comparative proteome profiling

Determination of cell type‐specific proteome signatures of primary human leukocytes, endothelial cells, keratinocytes, hepatocytes, fibroblasts and melanocytes by comparative proteome profiling

Identification of cardiovascular risk factors associated with bone marrow cell subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME and LateTIME clinical trials

Immunophenotyping Reveals the Diversity of Human Dental Pulp Mesenchymal Stromal Cells In vivo and Their Evolution upon In vitro Amplification

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