Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study.
BACKGROUND
Endothelial progenitor cells play an important role in vascular wall repair. Patients with type 1 diabetes have reduced levels of endothelial progenitor cells of which their functional capacity is impaired. Reduced nitric oxide bioavailability and increased oxidative stress play a role in endothelial progenitor cell dysfunction in these patients. Folic acid, a B-vitamin with anti-oxidant properties, may be able to improve endothelial progenitor cell function. In this study, we investigated the gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes compared to endothelial progenitor cells from healthy subjects. Furthermore, we studied the effect of folic acid on gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes.


METHODS
We used microarray analysis to investigate the gene expression profiles of endothelial progenitor cells from type 1 diabetes patients before (n = 11) and after a four week period of folic acid supplementation (n = 10) compared to the gene expression profiles of endothelial progenitor cells from healthy subjects (n = 11). The probability of genes being differentially expressed among the classes was computed using a random-variance t-test. A multivariate permutation test was used to identify genes that were differentially expressed among the two classes. Functional classification of differentially expressed genes was performed using the biological process ontology in the Gene Ontology database.


RESULTS
Type 1 diabetes significantly modulated the expression of 1591 genes compared to healthy controls. These genes were found to be involved in processes regulating development, cell communication, cell adhesion and localization. After folic acid treatment, endothelial progenitor cell gene expression profiles from diabetic patients were similar to those from healthy controls. Genes that were normalized by folic acid played a prominent role in development, such as the transcription factors ID1 and MAFF. Few oxidative-stress related genes were affected by folic acid.


CONCLUSIONS
Folic acid normalizes endothelial progenitor cell gene expression profiles of patients with type 1 diabetes. Signaling pathways modulated by folic acid may be potential therapeutic targets to improve endothelial progenitor cell function.
van Oostrom
Olivia
O
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands. o.vanoostrom@umcutrecht.nl
de Kleijn
Dominique P V
DP
Fledderus
Joost O
JO
Pescatori
Mario
M
Stubbs
Andrew
A
Tuinenburg
Attie
A
Lim
Sai Kiang
SK
Verhaar
Marianne C
MC
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D055018:Hemangioblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D013382:Subtraction Technique
D005492:Folic Acid
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