Although the contributions of sitagliptin to endothelial function in diabetes mellitus were previously reported, the potential mechanisms still remain undefined. Our research was intended to explore the underlying mechanisms of protective effects of sitagliptin treatment on endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male lean nondiabetic Zucker rats were used as control and male obese ZDF rats were randomly divided into ZDF and ZDF + sitagliptin groups. The significant decrease in endothelium-dependent relaxation induced by acetylcholine was observed in mesenteric arteries and thoracic aorta rings of ZDF rats. The administration of sitagliptin restored the vascular function effectively. The morphology study showed severe endothelial injuries in thoracic aortas of ZDF rats, and sitagliptin treatment attenuated these changes. The increased malondialdehyde levels and decreased superoxide dismutase activities in serum of ZDF rats were reversed by sitagliptin treatment. Sitagliptin also increased the expression of endothelial nitric oxide synthase and microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of inducible nitric oxide synthase, 3-nitrotyrosine, and p62 in ZDF rats. After giving Fe (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride porphyrin pentachloride (FeTMPyP, a peroxynitrite [ONOO] scavenger) or sitagliptin to high-glucose (30 mmol/L, 48 hours) cultured human umbilical vein endothelial cells (HUVECs), the increased levels of Beclin-1 and lysosome-associated membrane protein type 2 were detected. Both FeTMPyP and sitagliptin also significantly increased the number of mRFP-GFP-LC3 dots per cell, suggesting that autophagic flux was increased in HUVECs. Our study indicated that sitagliptin treatment can improve the endothelium-dependent relaxation and attenuate the endothelial impairment of ZDF rats. The protective effects of sitagliptin are possibly related to antiperoxynitrite and promoting autophagy.

Dipeptidyl-peptidase-4 (DPP-4) inhibitors, as the most recent available anti-diabetic agents, were generally used in clinical treatment of type 2 diabetes (T2DM). In addition to anti-diabetic effects, the five most widely used DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) also exert cardiovascular protective effects. In recent years, increasing studies suggest that sitagliptin shows pleiotropic impacts towards the cardiovascular system either with or without diabetes. In this review, we summarized the recent reports to provide an update discussion about cardiovascular protective effects of sitagliptin and the corresponding mechanisms. Sitagliptin has positive effects towards ischaemic cardiovascular diseases, atherosclerosis and hypertension. These effects are mainly conducted through DPP-4 inhibitions. In addition, sitagliptin exerts anti-inflammation, anti-oxidative stress, anti-apoptosis, mediation on lipid accumulation and so on, which also contribute to its cardiovascular effects.

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Background:Left ventricle diastolic malfunction (LVDMf) is a valvular cardiovascular disease. Here, we assessed the correlation between right ventricle (RV) load and function (L&F) and diastolic malfunction (DMf) in symptomless valvular cardiovascular disease patients. Material/Methods:We enrolled 59 subjects who underwent right-heart catheterization, assessing their echocardiographic analysis results while performing exercises in supine position, comparing results at rest and during maximum exercise. Subjects were furthermore stratified according to resting DMf. Using cardiac resonance imaging (CRM), we assessed cardiac morphology and chamber size. RV stroke, pulmonary artery conformation, pulmonary artery elastance, pulmonary artery pulsatility, and right atrial (pRA) pressure were indexed for supine exercises. Results:We observed that DMf grade 1 (G-1) and grade 2 (G-2) were present in 28 patients and 16 patients, respectively, while the remaining 15 patients had a normal filling pattern in the left ventricle. In comparison to patients with DMf of G-1, patients with normal diastolic filling pattern had higher volume index for RV end-diastolic (endD) (81±14 mL/m 2 vs. 68±12 mL/m 2 , P=0.08) and for RV end-systolic (endS) (34±11 mL/m 2 vs. 27±8 mL/m 2 , P=0.07). We also observed that in G-2 DMf pulmonary artery, pressure and elastance of the pulmonary artery were enhanced and were correlated with optimum oxygen intake and RV volume (r=-0.69, P<0.001). Conclusions:We found that enhancement in RV afterload, which returns to normal at rest, is correlated with mild DMf. Additionally, despite maximum exercise, it is reciprocally associated with maximum oxygen intake and right atrial pressure.

Objective : To investigate the imaging characteristics of ultrasound and magnetic resonance imaging in extra-abdominal desmoid-type fibromatosis. Methods : Ultrasonic images of 58 patients with extra-abdominal desmoid-type fibromatosis and MRI images of 59 patients with extra-abdominal desmoid-type fibromatosis were analyzed retrospectively. The imaging characteristics of the two methods in the diagnosis of extra-abdominal desmoid-type fibromatosis were analyzed. Results : Among the 58 patients detected by ultrasound, obvious strong cord-like, columnar, and flocculent echoes were seen in 50 patients; blood flow signal was abundant in 37 patients. Among the 59 patients detected by MRI, fat-suppressed sequence scanning mainly presented high signal intensities. Spot-like and cordlike low signal intensities could be seen in lesions. Enhancement was obvious in 59 patients. In 58 patients detected by ultrasound, preoperative tumor diameter (4.46 ± 1.95) cm was shorter than the postoperative pathological result (6.33 ± 1.32) cm ( P < 0.05). In 59 patients detected by MRI, no significant difference in tumor diameter was detectable between preoperative (6.17 ± 0.98) cm and postoperative (6.32± 0.77) cm results ( P > 0.05). Conclusion : Ultrasound can reveal the fiber composition of desmoid-type fibromatosis well. MRI has certain advantages in diagnosing the true size and invasion range of desmoid-type fibromatosis, and can provide imaging reference for preoperative and postoperative evaluation.