Microvascular adaptation to metabolic stress is important in the maintenance of tissue homeostasis. Nowhere is this more important than in the central nervous system (CNS) where the cellular constituents of the neurovascularture including endothelial cells, pericytes and some astroglia must make fine-tuned autoregulatory modulations that maintain the delicate balance between
oxygen availability and metabolic demand.
miRNAs have been reported to play an important regulatory role in many cellular functions including cell differentiation, growth and proliferation, lineage determination, and metabolism. In this study, we investigated the possible role of
miRNAs in the CNS capillary pericyte response to hypoxic stress. Micro-array analysis was used to examine the expression of 388 rat
miRNAs in primary rat cortical pericytes with and without exposure to low
oxygen (1%) after 24 or 48 hr. Pericytes subjected to
hypoxia showed 27
miRNAs that were higher than control and 31 that were lower. Validation and quantification was performed by Real Time RT-PCR on pericytes subjected to 2 hr, 24 hr, or 48 hr of
hypoxia.
Hypoxia induced changes included physiological pathways governing the stress response, angiogenesis, migration and cell cycle regulation.
miRNAs associated with HIF-1α (miR-322[1], miR-199a [2]), TGF-β1 (miR-140[3], miR-145[4], miR-376b-3p[5]) and
VEGF (miR-126a[6], miR-297[7], miR-16[8], miR-17-5p[9]) were differentially regulated. Systematic and integrative analysis of possible gene targets analyzed by DAVID bioinformatics resource (http://david.abcc.ncifcrf.gov) and MetaSearch 2.0 (GeneGo) for some of these
miRNAs was conducted to determine possible gene targets and pathways that may be affected by the post-transcriptional changes after hypoxic insult.