Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension

Asosingh, Kewal; Aldred, Micheala A.; Vasanji, Amit; Drazba, Judith A.; Sharp, Jacqueline; Farver, Carol; Comhair, Suzy; Xu, Weiling; Licina, Lauren; Huang, Lan; Anand‐Apte, Bela; Yoder, Mervin C.; Tuder, Rubin M.; Erzurum, Serpil C.

doi:10.2353/ajpath.2008.070705

Cited by 160 publications

(179 citation statements)

References 64 publications

Supporting

Mentioning

171

Contrasting

Unclassified

Order By: Relevance

“…4 While some subsets of proangiogenic hematopoietic cells, including CD34 ϩ CD133 ϩ cells, are vital promoters of angiogenesis in human health and disease, 5 CD34 ϩ CD133 ϩ progenitor cells have been reported to circulate in significantly greater numbers in patients with PAH and to correlate with severity of disease and to demonstrate greater proliferative potential. 6 Farha and colleagues confirmed the higher circulating concentrations of CD34 ϩ CD133 ϩ cells in insideblood PAH patients and also reported higher concentrations of these cells in patient bone marrowaspirates (see figure). In those marrow samples, CD34 ϩ CD133 ϩ cells displayed higher clonogenic proliferation and increased myeloid colony forming activity.…”

supporting

confidence: 56%

Bad blood, bad endothelium: ill fate?

Yoder

Rounds

2011

Blood

View full text Add to dashboard Cite

supporting

confidence: 56%

Bad blood, bad endothelium: ill fate?

Yoder

Rounds

2011

Blood

View full text Add to dashboard Cite

“…However, the role of these circulating cells in biomarker discovery and their potential contribution to the pathobiology of SCD and PAH have both been well established (8,10,26,27). Circulating blood cells may carry disease-specific information due to genetics or due to alterations in their local environment.…”

Section: Discussionmentioning

confidence: 99%

A Novel Molecular Signature for Elevated Tricuspid Regurgitation Velocity in Sickle Cell Disease

Desai¹,

Zhou²,

Ahmad

et al. 2012

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: An increased tricuspid regurgitation jet velocity (TRV . 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD). Objectives: We explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD. Methods: Twenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms. Measurements and Main Results: Genome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n ¼ 10) and with pulmonary hypertension (n ¼ 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n ¼ 49) versus normal (n ¼ 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P , 0.005), four trans-acting (P , 2.1 3 10 27) and one cis-acting (P ¼ 0.6 3 10 24 ) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B). Conclusions: These studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.

show abstract

“…Many recent studies and reviews discuss the properties of pro-angiogenic cell populations or 'circulating angiogenic cells' in depth (Case et al, 2007;Timmermans et al, 2007Timmermans et al, , 2008Hirschi et al, 2008;Gao et al, 2009;Yoder and Ingram, 2009). A specific role of CD133 þ /HPCs has been suggested in pulmonary vascular remodelling in patients with obstructive pulmonary disease (Asosingh et al, 2008) or idiopathic pulmonary arterial hypertension (Diez et al, 2007). Thus, it seems plausible that the production and release of cytokines, chemokines and proteolytic enzymes (VEGF, SDF-1 and metalloproteases) by the lung tumour tissue will increase the mobilisation of CD133 þ /HPCs from the bone marrow, which may be home to hypoxic tumour tissue and have a fundamental role in tumour neovascularization and progression (Kerbel, 2008;Shojaei and Ferrara, 2008).…”

Section: Discussionmentioning

confidence: 99%

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

et al. 2009

View full text Add to dashboard Cite

Background: Blood-based biomarkers may be particularly useful for patient selection and prediction of treatment response for angiogenesis inhibitors. Circulating endothelial cells (CECs) and haematopoietic progenitor cells (HPCs) might have a role in tumour angiogenesis and in tumour growth. Measurement of CECs and HPCs in the blood of patients could be a simple, non-invasive way to monitor or predict responses to treatment. Methods: (VEGFR2 + ) CECs , (CD133 + ) HPCs, plasma vascular endothelial growth factor (VEGF) and erythropoietin were measured in blood from 25 non-small cell lung cancer (NSCLC) patients before and during treatment with sorafenib plus erlotinib (SO/ER). In order to assess the drug specificity of changes in CECs and HPCs, 18 patients treated with bevacizumab plus erlotinib (BV/ER) and 10 patients with erlotinib (ER) monotherapy were studied. Response was measured in all patient groups by Response Evaluation Criteria in Solid Tumors (RECIST). Results: At day 7, SO/ER-treated patients showed a three-fold increase in CECs ( P <0.0001) comparable to BV/ER-treated patients ( P <0.01), and the CECs did not change with erlotinib treatment ( P =0.8). At day 7, CD133 + /HPCs decreased with SO/ER treatment ( P <0.0001). HPC numbers did not change with either BV/ER or erlotinib. In SO/ER-treated patients pre-treatment CD133 + /HPCs were significantly lower in responders ( P =0.01) and pre-treatment CD133 + /HPC numbers lower than the median correlated with a longer time-to-progression (TTP) ( P =0.037). Conclusion: Pre-treatment CD133 + /HPCs are a promising candidate biomarker to further explore for use in selecting NSCLC patients who might benefit from SO/ER treatment.

show abstract

Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension

Cited by 160 publications

References 64 publications

Bad blood, bad endothelium: ill fate?

Bad blood, bad endothelium: ill fate?

A Novel Molecular Signature for Elevated Tricuspid Regurgitation Velocity in Sickle Cell Disease

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

Contact Info

Product

Resources

About