Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats.
Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats.
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DOI：
10.1186/1475-2840-13-43
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发表时间：
2014-02-13
影响因子：
9.3
通讯作者：
Ito H
中科院分区：
文献类型：
--
作者：
Miyoshi T;Nakamura K;Yoshida M;Miura D;Oe H;Akagi S;Sugiyama H;Akazawa K;Yonezawa T;Wada J;Ito H
伴有左心室肥厚的心力衰竭通常与胰岛素抵抗和炎症有关。最近的研究表明，二肽基肽酶4(DPP4)抑制剂可以改善糖代谢和炎症状态。因此，我们评估了DPP4抑制剂维达格列汀是否能预防异丙肾上腺素治疗的大鼠左室肥厚和改善舒张期功能。雄性Wistar大鼠分别给予Vile1(n = 2 0)、皮下异丙肾上腺素(2.4 mg/kg/d，n = 2 0)、皮下异丙肾上腺素(2.4 mg/kg/d，n = 2 0)或Vo-VL(Ver-VL)(30 mg/kg/d，n = 2 0)，共7天。4组间血压差异无统计学意义(P>0.05)，而VL组左室肥厚明显低于异丙组(心脏重量/体重，Vehicle：3.2 ± 0.40，Iso：4.43 ± 0.39，Iso-VL：4.14 ± 0.29，Vehicle-VL：3.16 ± 0.16，p <； 0.05)。心导管检查显示，维达格列汀降低了ISO组升高的LV舒张末压力，但ISO-VL组的其他有关LV舒张期功能的参数，如降低的最小dp/dt并没有改善。组织学分析显示，维达格列汀可减轻心肌细胞肥大和血管周围纤维化，但不影响心肌组织血管生成。定量聚合酶链式反应显示，异丙肾上腺素组大鼠心肌中肿瘤坏死因子α、白介素6、胰岛素样生长因子L的表达减弱，葡萄糖转运蛋白4型的表达降低。维达格列汀可预防异丙肾上腺素所致的大鼠左室肥厚。
Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p < 0.05). Cardiac catheterization revealed that vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats.
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影响因子：
7.7
作者：
Kim, Su-Jin;Nian, Cuilan;Doudet, Doris J.;McIntosh, Christopher H. S.
通讯作者：
McIntosh, Christopher H. S.
影响因子：
9.3
作者：
Miki T;Itoh T;Sunaga D;Miura T
通讯作者：
Miura T
影响因子：
5
作者：
Giannocco, Gisele;Oliveira, Kelen C.;Girardi, Adriana C. C.
通讯作者：
Girardi, Adriana C. C.
DOI：
10.1152/ajpregu.2001.280.6.r1823
发表时间：
2001-06-01
影响因子：
2.8
作者：
Gallego, B;Arévalo, MA;Pérez-Barriocanal, F
通讯作者：
Pérez-Barriocanal, F
影响因子：
37.8
作者：
Murray, DR;Prabhu, SD;Chandrasekar, B
通讯作者：
Chandrasekar, B