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    The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model
    (Turkish Soc Cardiology, 2011) Guzeloglu, Mehmet; Gul, Mehmet; Reel, Buket; Yurekli, Ismail; Aykut, Koray; Hazan, Eyup
    Objective: The aim of the present study was to investigate the effect of zoledronic acid (ZA), as a matrix metalloproteinase inhibitor, on neointimal hyperplasia in rabbit carotid anastomosis model. Methods: New Zealand male rabbits were divided into two groups as placebo and treatment groups in this experimental study. After anesthesia, the right carotid artery of each rabbit was end-to-end anastomosed with an 8/0 polypropylene suture. Left carotid artery was kept as control without any operation. Placebo group (n=6) received phosphate buffered saline (PBS) (0.5mL/kg/day/s.c.) for 28 days postoperatively, whereas ZA group (n=6) received ZA (100 mu g/kg/day/s.c.) for the same period. After sacrification, the anastomosed and control arteries were isolated. Morphometric and immunohistochemical examinations were performed. Statistical analyses of morphometric and immunohistochemical data were performed using two-way ANOVA and Chi-square test respectively. Results: In PBS group, vascular injury in the anastomosed artery significantly increased the intimal area (anastomosed: 112.51 +/- 61.18 mu m(2)*1000 vs. control: 22.62 +/- 4.26 mu m(2)*1000, p<0.01) and intima/media index (anastomosed: 0.347 +/- 0.29 vs. control: 0.075 +/- 0.01, p<0.05) compared to control artery. ZA significantly reduced the intimal area (39.29 +/- 18.21 mu m(2)*1000, p<0.01) and intima/media index (0.112 +/- 0.07, p<0.05) compared to PBS group. Additionally, a-smooth muscle actin immunopositivity was found significantly decreased in anastomosed arteries from ZA group (ZA: 2.33 +/- 0.52 vs. PBS: 3.50 +/- 0.5, p<0.05). Moreover, intensive gelatinase (MMP-2 and MMP-9) immunoreactivities were clearly seen in anastomosed arteries compared to control arteries from PBS group. ZA apparently decreased immunopositivities for gelatinases in anastomosed arteries. Conclusion: ZA might be a promising agent for prevention of neointimal hyperplasia, which is the most significant cause of graft failures in late postoperative period. (Anadolu Kardiyol Derg 2011; 11: 93-100)
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    The low levels of bone morphogenic protein-4 and its antagonist noggin in type 2 diabetes
    (Springer International Publishing Ag, 2018) Yurekli, Banu Sarer; Kocabas, Gokcen Unal; Aksit, Murat; Kutbay, Nilufer Ozdemir; Suner, Asli; Yurekli, Ismail; Cakir, Habib; Bozkaya, Giray; Cetinkalp, Sevki
    Objective Bone morphogenic protein-4 (BMP-4) is a proinflammatory cytokine which is controlled by BMP-4 antagonists. Our aim was to investigate the levels of BMP-4 and its antagonists, noggin and matrix Gla protein (MGP), in prediabetes and diabetes. Design One hundred and forty-two type 2 diabetic, 32 prediabetic, and 58 control subjects participated in this cross-sectional study. BMP-4, noggin, and MGP were measured with the ELISA method. Results There was a significant difference between the three groups in relation to sex, hypertension, fasting plasma glucose, HbA1c, lipid profiles, and diastolic blood pressure (p < 0.05). BMP-4 levels were significantly lower in the diabetic group compared to the control group (108.5 and 127.5 ng/mL, respectively, p < 0.001 diabetes vs. control). Noggin levels were significantly lower in the diabetic group compared to the prediabetic and control groups (10.5, 11.5, and 12.0 ng/mL, as median, respectively, p < 0.001; diabetes vs. control, p = 0.002; diabetes vs. prediabetes). BMP-4 was associated significantly with noggin in the entire study population (beta coefficient = 0.796, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve was 0.708 (95% CI 0.551-0.864, p = 0.011) for BMP-4 levels. The optimal cutoff value of BMP-4 for detecting albuminuria was 118.5 ng/mL for which sensitivity was 71.4% and specificity was 66.4%. Conclusions BMP-4 and noggin levels were lower in the diabetic group. High BMP-4 levels were significantly associated with albuminuria. Further studies are warranted to determine the role of BMP-4 in the pathogenic processes underlying albuminuria and hyperglycemia in patients with type 2 diabetes.