Upregulated hypoxia inducible factor-1α and -2α pathway in rheumatoid arthritis and osteoarthritis

Giatromanolaki, Alexandra; Sivridis, Efthimios; Maltezos, Efstratios; Athanassou, Nick; Papazoglou, Dimitrios; Gatter, Kevin C.; Harris, Adrian L.; Koukourakis, Michael I.

doi:10.1186/ar756

Cited by 168 publications

(48 citation statements)

References 46 publications

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“…It can be hypothesized that the association of the VEGFR2 His472Gln polymorphism with muscle Wbre composition may be attributable to the autocrine interaction between VEGFR2, VEGF, erythropoietin (EPO) and HIF1 factors. Although HIF1 is a transcriptional regulator of genes encoding EPO, VEGF and VEGF receptors (Semenza 2000), expression of these factors is also inter-related (Sivridis et al 2002;Calvani et al 2008;Giatromanolaki et al 2003Giatromanolaki et al , 2008Tam et al 2006). HIF1 has been also shown to regulate muscle Wbre composition, presumably via regulation of EPO and glycolytic genes.…”

Section: Discussionmentioning

confidence: 97%

Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes

et al. 2009

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Vascular endothelial growth factor receptor 2 (VEGFR2) is essential to induce the full spectrum of VEGF angiogenic responses to aerobic training. In the present study, we examined the impact of the functional His472Gln polymorphism of the VEGFR2 gene on elite athlete status, endurance performance and muscle fibre type composition. Four hundred and seventy-one Russian athletes were prospectively stratified into four groups according to event duration, distance and type of activity, covering a spectrum from the more endurance-oriented to the more power-oriented. VEGFR2 genotype and allele frequencies were compared to 603 controls. To examine the association between VEGFR2 genotype and fibre type composition, vastus lateralis muscle biopsies were obtained from 45 physically active healthy men and 23 all-round speed skaters. In addition, 76 competitive rowers performed incremental endurance exercise to allow analysis of genotype associations with exercise responses. We found that the frequency of the VEGFR2 472Gln allele was significantly higher in endurance-oriented athletes compared to controls (36.8 vs. 27.4%, P = 0.0006). Relative VO(2max) was significantly greater in the VEGFR2 472Gln allele carriers compared with the His/His homozygotes of the sub-elite female rower group only. Genotype-specific differences were found for the proportion of slow-twitch fibres in both athletes and controls, which was approximately 10.1 and approximately 7.4% higher in the His/Gln and Gln/Gln genotypes than in the His/His genotype group, respectively. In conclusion, we have shown for the first time that variation in the VEGFR2 gene is associated with elite athlete status, endurance performance of female rowers and muscle fibre type composition.

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Section: Discussionmentioning

confidence: 97%

Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes

et al. 2009

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“…18,19) In addition to the increase in CDK inhibitor mRNAs, transcripts for heat shock protein (HSP), HSP27, HSP40, HSP70, HSP90b and HSC70, and HIF-1a were higher in the GFL than in the PNM region. [20][21][22] The levels of these transcripts were much higher in CD patients than those in the normal colon. These results indicate that GFL regions could be experiencing hypoxia.…”

Section: Comparison Of Transcript Changes Found In Tnbs Treated Mice mentioning

confidence: 99%

Intestinal Gene Expression in TNBS Treated Mice Using GeneChip and Subtractive cDNA Analysis: Implications for Crohn's Disease

Yamamoto

Isuzugawa

Takahashi

et al. 2005

Biological & Pharmaceutical Bulletin

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So far it has proven difficult to identify a causative gene(s) or gene product initiating the events that lead to inflammation of the intestinal mucosa and, ultimately, progression to Crohn's disease (CD), an inflammatory bowel disease. However, gene transcripts identified in the intestine of trinitrobenzene sulfonic acid (TNBS)-treated mice might suggest a clue, and even represent candidate genes leading to inflammation and mucosal damage, and to subsequent fibrosis. In the present study, DNA microarray (13000 transcripts) methodology was applied to mucosal RNA extracted from TNBS-treated mice, some transcripts of which were validated via cDNA subtraction and RT-PCR analyses. Intestinal biopsy samples from CD patients were then analyzed using cDNA mini-array (1300 cDNAs), focusing on gene transcripts associated with cancer and immunity. Mini-array results revealed transcript changes similar and also dissimilar to those found from the DNA microarray analysis. These changes, previously known or newly identified, possibly occurring during the initial and progressive stages of inflammatory conditions may provide a clue to identify marker transcripts and/or targets for the development of future gene therapy.

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“…Hypoxia inducible factors (HIF-1α and HIF-2α) have been implicated in angiogenesis, as they are essential in regulating the transcription of the VEGF gene. HIF-mediated inflammatory and angiogenic pathways are involved in RA [39]. Among pro-inflammatory cytokines, TNF-α, IL-1, IL-6, IL-8, IL-15 and IL-18 are involved in angiogenesis [27][28][29][30][31][32][33][34][35]40,41).…”

Section: Endothelial Cells In Angiogenesismentioning

confidence: 99%

Endothelial Cells in Inflammation and Angiogenesis

Szekanecz¹,

Koch

2005

CDTIA

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Endothelial cells are involved in leukocyte extravasation underlying inflammation. A number of adhesion molecules play a role in leukocyte-endothelial interactions. New vessel formation, termed angiogenesis, is also crucial for leukocyte extravasation. The outcome of neovascularization is highly dependent on the balance or imbalance between angiogenic mediators and inhibitors. There have been several attempts to therapeutically interfere with the cellular and molecular mechanisms, such as leukocyte-endothelial cell adhesion and angiogenesis. Most studies have been performed using animal models of various types of inflammation, such as arthritis. In addition, a very limited number of human clinical trials gave promising results. In this review, authors summarize the most relevant information on adhesion molecules, as well as angiogenic and angiostatic agents. In addition, further perspectives of anti-adhesive and anti-angiogenic therapy are also discussed. Specific targeting of pathological endothelial function including adhesion and angiogenesis, may be useful for the future management of various inflammatory diseases.

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Upregulated hypoxia inducible factor-1α and -2α pathway in rheumatoid arthritis and osteoarthritis

Cited by 168 publications

References 46 publications

Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes

Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes

Intestinal Gene Expression in TNBS Treated Mice Using GeneChip and Subtractive cDNA Analysis: Implications for Crohn's Disease

Endothelial Cells in Inflammation and Angiogenesis

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