ABSTRACT
OBJECTIVES: Mesenchymal stem cells are viewed as the first choice in regenerative medicine. This study aimed to elucidate the influence of BM-MSCs transplantation on angiogenesis in a rat model of unilateral peripheral vascular disease. MATERIALS AND METHODS: Twenty-one rats were arbitrarily allocated into three groups (7/group). Group I: control sham-operated rats, Group II: control ischemic group: Rats were subjected to unilateral surgical ligation of the femoral artery, and Group III: ischemia group: Rats were induced as in group II, 24 hr after ligation, they were intramuscularly injected with BM-MSCs. After scarification, gastrocnemius muscle gene expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor receptor 2 (VEGFR2), von Willebrand factor (vWF), and hypoxia-inducible factor-1α (HIF-1α) were analyzed by quantitative real-time PCR. Muscle regeneration and angiogenesis evaluation was assessed through H&E staining of the tissue. Furthermore, Pax3 and Pax7 nuclear expression was immunohistochemically assessed. RESULTS: Rats treated with BM-MSCs showed significantly raised gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF compared with control and ischemia groups. H&E staining of the gastrocnemius showed prominent new vessel formation. Granulation tissue within muscles of the ischemic treated group by BM-MSCs showed cells demonstrating nuclear expression of Pax3 and Pax7. CONCLUSION: BM-MSCs transplantation has an ameliorating effect on muscle ischemia through promoting angiogenesis, detected by normal muscle architecture restoration and new blood vessel formations observed by H&E, confirmed by increased gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF, decreased HIF-1α gene expression, and increased myogenic Pax7 gene expression.
ABSTRACT
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease. We aimed to measure the level of miR-155 and its genetic variant rs767649 in patients with RA and to evaluate their relationship with ischemia-modified albumin (IMA). The study was performed on 79 patients with RA (group I) and 78 healthy control participants (group II). Quantitative real-time polymerase chain reaction was used to assess the expression of serum miR-155 in addition to its functional variant rs767649. IMA levels were measured by enzyme-linked immunosorbent assay. Significant overexpression of miR-155 and higher levels of IMA were detected in patients with RA compared with those in controls (P < 0.0001). The fold change in miR-155 was significantly positively associated with IMA (r = 0.362, P = 0.001) in patients with RA. Significant differences in the frequency of miR-155 (rs767649) genotypes and alleles were noted between patients with RA and controls. MiR-155 and IMA levels were significantly associated with the genotype distribution of miR-155 (rs767649) in patients with RA and were higher in patients with the TT genotype. MiR-155 and its functional variant rs767649 might play an important role in susceptibility to the increased risk of RA, stressing the role of miR-155 as a therapeutic target in the treatment of RA. In addition, IMA levels were increased and correlated with miR-155 and its single nucleotide polymorphism rs767649 in Egyptian patients with RA.
