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Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).

ABSTRACT: BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major regulator of both physiological and pathological angiogenesis. Associations between polymorphisms in VEGFA and complex disease have been inconsistent. The parent from whom the allele was inherited may account for these inconsistencies. This study examined the parent of origin effect on the expression of murine Vegfa. METHODS: Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were crossed to produce reciprocal AJ129 and 129AJ offspring, respectively. RNA was extracted from cardiac tissue of 6 week old male (n = 8) and female (n = 8) parental, and male and female F1 offspring mice (AJ129 n = 8 and 129AJ n = 8). Vegfa and Hif1a expression levels were measured by qPCR and compared between the F1 offspring from the reciprocal crosses. RESULTS: We found significant differences in the expression of Vegfa in F1 offspring (AJ129 and 129AJ mice) of the reciprocal crosses between AJ and 129 mice. Offspring of male AJ mice had significantly higher expression of Vegfa than offspring of male 129 mice (p = 0.006). This difference in expression was not the result of preferential allele expression (allelic imbalance). Expression of Hif1a, a transcriptional regulator of Vegfa expression, was also higher in F1 offspring of an AJ father (p = 0.004). CONCLUSION: Differences in Vegfa and Hif1a gene expression are likely the result of an upstream angiogenic regulator gene that is influenced by the parent of origin. These results highlight the importance of including inheritance information, such as parent of origin, when undertaking allelic association studies.

SUBMITTER: Chiu CL

PROVIDER: S-EPMC3626619 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).

Chiu Christine L CL Morgan Chloe T CT Lupton Samantha J SJ Lind Joanne M JM

BMC medical genetics 20130405

<h4>Background</h4>Vascular endothelial growth factor A (VEGFA) is a major regulator of both physiological and pathological angiogenesis. Associations between polymorphisms in VEGFA and complex disease have been inconsistent. The parent from whom the allele was inherited may account for these inconsistencies. This study examined the parent of origin effect on the expression of murine Vegfa.<h4>Methods</h4>Two homozygous, inbred mouse strains A/J (AJ) and 129x1/SvJ (129) were crossed to produce r ...[more]

PMID: 23560444

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Project description:Vascular endothelial growth factor A (VEGFA) stimulates angiogenesis and is associated with increased vascularity in ovarian follicles of cattle. The objectives of this study were to investigate the developmental and hormonal regulation of VEGFA expression in ovarian granulosa and theca cells (TC) of cattle. Bovine ovaries were collected from a local slaughterhouse and granulosa cells (GC) and TC were collected from small (SM; 1 to 5 mm) and large (LG; 8 to 20 mm) follicles. Cells were collected fresh or cultured in serum-free medium and treated with various factors that regulate angiogenesis and follicular development. RNA was collected for analysis of VEGFA mRNA abundance via quantitative PCR. In SM-follicle GC (SMGC), prostaglandin E2 (PGE2) and FSH decreased (P < 0.05) VEGFA mRNA abundance by 30 to 46%, whereas in LG-follicle GC (LGGC), PGE2 and FSH were without effect (P > 0.10). In SMGC, dihydrotestosterone (DHT), sonic hedgehog (SHH), and growth differentiation factor-9 (GDF9) decreased (P < 0.05) VEGFA expression by 30 to 40%. Fibroblast growth factor-9 (FGF9) and estradiol (E2) were without effect (P > 0.10) on VEGFA mRNA in both SMGC and LGGC, whereas progesterone increased (P < 0.05) VEGFA mRNA in LGGC but had no effect in LGTC. Bone morphogenetic protein-4 (BMP4), LH, and FGF9 increased (P < 0.05) abundance of VEGFA mRNA by 1.5- to 1.9-fold in LGTC. Insulin-like growth factor-1 (IGF1) was without effect (P > 0.10) on VEGFA mRNA in both TC and GC. An E2F transcription factor inhibitor, HLM0064741 (E2Fi), dramatically (i.e., 8- to 13-fold) stimulated (P < 0.01) the expression of VEGFA mRNA expression in both SMGC and LGTC. Abundance of VEGFA mRNA was greater (P < 0.05) in LGGC and SMGC than in LGTC. Also, SMTC had greater (P < 0.05) abundance of VEGFA mRNA than LGTC. In conclusion, VEGFA mRNA abundance was greater in GC than TC, and VEGFA expression decreased in TC during follicle development. Some treatments either suppressed, stimulated, or had no effect on VEGFA expression depending on the cell type. The inhibition of E2F transcription factors had the greatest stimulatory effect of all treatments evaluated, and thus, E2Fs may play an important role in regulating angiogenesis during follicle growth in cattle.

Project description:BackgroundInfantile hemangioma (IHA) is the most common tumor in infancy. We aimed to explore the effect of propranolol on the expression of microRNA (miR)-424 in IHA tissues and XPTS-1 cells, as well as its molecular mechanism of inhibiting XPTS-1 cell activity.MethodsTumor tissues and peritumoral tissue were collected from 13 IHA patients in Lishui Municipal Central Hospital. The level of miR-424 were detected using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Cell counting kit-8 (CCK-8) was used to measure XPTS-1 cell viability. Flow cytometry and transwell were used to detect the apoptosis level and invasion ability of XPTS-1 cells. Western blot was used to measure the protein level of vascular endothelial growth factor-A (VEGFA). The luciferase reporter gene assay detected the targeting relationship between miR-424 and VEGFA.ResultsCompared with normal tissues and human umbilical vein endothelial cells, the expression level of miR-424 in IHA tissues and XPTS-1 cells was significantly reduced (P<0.05). As the concentration of propranolol increased, XPTS-1 cell viability gradually decreased (P<0.05), and the expression level of VEGFA decreased (P<0.05). The expression of miR-424 increased with the time of propranolol treatment (P<0.05). Compared with the control group, treatment with an miR-424 inhibitor resulted in a significant increase in XPTS-1 cell viability and invasion ability (P<0.05), and a decrease in apoptosis (P<0.05). However, both propranolol and miR-424 inhibitor treatment resulted in a partial decrease in XPTS-1 cell viability (P<0.05), and a partial increase in the level of apoptosis (P<0.05). MiR-424 directly targeted VEGFA; the overexpression of miR-424 resulted in a decrease in the VEGFA protein level (P<0.05), while inhibition of miR-424 resulted in an increase in the VEGFA protein level (P<0.05). Compared with the propranolol group, the XPTS-1 cell viability and invasion ability in the propranolol + VEGFA-si group were significantly decreased (P<0.05), while the level of apoptosis increased (P<0.05). Meanwhile, simultaneous miR-424 inhibitor treatment resulted in no difference in cell viability and apoptosis levels compared with the propranolol group, and the invasion ability was partially restored (P<0.05).ConclusionsPropranolol affects the malignant biological behavior of IHA cells by regulating the miR-424/VEGFA axis.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is characterized by the growth of a number of small cysts on the ovaries which leads to sex hormonal imbalance. Women who are affected by this syndrome suffer from irregular menstrual cycles, decline in their fertility, excessive hair growth, obesity, acne and most importantly cardiac function problems. The vascular endothelial growth factor (VEGF) plays a pivotal role in tissue vascularization in general and in the pathogenesis of many diseases. The PCOS was found to be associated with high expression levels of VEGF. In women who undergo assisted reproductive procedures (ART), VEGF was found to be a key mediator of other factors to control ovary angiogenesis. Here, we set out to examine the association of VEGFA gene polymorphism with PCOS and its components in a population of Tunisia women to enhance our understanding of the genetic background leading angiogenesis and vascularization abnormalities in PCOS.MethodsThe association of VEGFA gene with PCOS and its components was examined in a cohort of 268 women from Tunisia involving 118 PCOS patients and 150 controls. VEGFA gene variations were assessed through the analysis of the following SNPs rs699947 (A/C), rs833061 (C/T), rs1570360 (G/A), rs833068 (G/A), rs3025020 (C/T), and rs3025039 (C/T). The linkage disequilibrium between SNPs was assessed using HAPLOVIEW software while combination of SNPs into haplotypes in the population and the reconstruction of the cladogram were carried-out by PHASE and ARLEQUIN programs, respectively. Genetic association and genotype-phenotype correlations were calculated by logistic regression and non-parametric tests (Kruskall-Wallis and Mann-Whitney tests), respectively, using StatView program.ResultsWe observed 10 haplotypes in our studied cohort whereH1 (ACGG), H2 (ACAG), H7 (CTGG) and H8 (CTGA) were the most frequent. We observed the association of the genotype CT of the SNP rs30225039 with PCOS phenotype (P = 0.03; OR 95 % CI = 2.05 [1.07-3.90]) and a trend for correlation of the pair of haplotypes H2/H2 with prolactin levels in plasma (P = 0.077; 193.5 ± 94.3 vs 45.7 ± 7.2). These data are consistent with literature and highlight one more time the role of vascularization in the pathogeny of PCOS.ConclusionsLD pattern in VEGF locus showed a similar LD pattern between the Tunisian population and the CEU. More haplotypes in the Tunisian population than in CEU was observed (22 haplotypes vs 16 haplotypes) suggesting higher recombination rate in Tunisians. The study showed that there was any advantage of using haplotypes compared with SNPs taken alone.

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Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).

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Parent of origin influences the cardiac expression of vascular endothelial growth factor (Vegfa).

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