Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas

Background: Leiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas. Methods: Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography. Results: Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p < 0.001, p = 0.004, p = 0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p = 0.021) as well as MMP-9 (p = 0.001) peripheral levels in the patient's group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues. Conclusions: This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance

MicroRNAs: Novel Diagnostic and Prognostic Biomarkers in Atherosclerosis

MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. The involvement of miRNAs in the regulation of lipid metabolism, inflammatory response, cell cycle progression and proliferation, oxidative stress, platelet activation, endothelial function, angiogenesis and plaque formation and rapture indicates important roles in the initiation and progression of atherosclerosis. In the light of this evidence we will review the role of miRNAs in atherosclerosis

Association of Sarcoidosis With Endothelial Function, Arterial Wall Properties, and Biomarkers of Inflammation

BACKGROUND Sarcoidosis is an inflammatory disease, which may affect vascular function. The study was designed to assess the impact of sarcoidosis on endothelial function and arterial stiffness. METHODS Eighty-seven sarcoidosis patients and eighty-seven matched healthy subjects (CI) were included in the study. Sarcoidosis patients were divided into two groups. Group 1 included patients never treated and group 2 included patients receiving cortisone treatment. Endothelial function was evaluated by flow-mediated dilatation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (A175) as a measure of arterial wave reflections. Serum levels of soluble intercellular adhesion molecule-1 and tumor necrosis factor-alpha (TNF-alpha), were measured. RESULTS In the totality of the population, sarcoidosis patients had significantly lower FMD (P < 0.01) and significantly higher A175 (P < 0.05). There was also a significant difference, between group 1, and Cl in FMD and A175, but there was no difference between group 2 and CI in FMD and A175. A175 values were significantly correlated with serum levels of intercellular adhesion molecule-1 (ICAM-1) (r = 0.370, P < 0.01) and TNF-alpha (r = 0.219, P = 0.049). CONCLUSIONS In the present study, we have shown that sarcoidosis patients have impaired endothelial function and increased arterial stiffness. Sarcoidosis patients on cortisone treatment had no differences compared to controls on the vascular parameters. Moreover, there was a significant correlation between inflammatory process and vascular function impairment. These findings indicate that sarcoidosis patients have impaired vascular function and increased inflammatory status, which may improve with cortisone treatment