Impact of Renal Artery Stent Implantation on Hypertension in Patients with Hemodialysis

The benefit from renal artery stent implantation to treat atherosclerotic renal artery stenosis (ARAS) is not well understood in hemodialysis patients. We sought to evaluate the effects of renal artery stenting on hypertension of hemodialysis patients. Renal artery stent implantation was successfully performed on eight hypertensive hemodialysis patients with ARAS (mean ± SD, 66 ± 10 years; men 6, women 2). Blood pressure was measured by automated oscillometric recordings just before hemodialysis. Mean values of the blood pressure, measured 12 times a month, were used for blood pressure analysis. Values of systolic blood pressure decreased at 6 months after renal artery stent implantation (162.6 ± 29.7 to 121.1 ± 23.3 mm Hg, p = 0.0015). Values of diastolic blood pressure also decreased from 77.6 ± 13.6 to 65.6 ± 7.2 mm Hg (p = 0.02). Renal artery stent implantation for ARAS had a beneficial effect on hypertension in hemodialysis patients.     

Rhein Protects Pancreatic β-Cells From Dynamin-Related Protein-1–Mediated Mitochondrial Fission and Cell Apoptosis Under Hyperglycemia

Rhein, an anthraquinone compound isolated from rhubarb, has been shown to improve glucose metabolism disorders in diabetic mice. The mechanism underlying the protective effect of rhein, however, remains unknown. Here, we demonstrate that rhein can protect the pancreatic β-cells against hyperglycemia-induced cell apoptosis through stabilizing mitochondrial morphology. Oral administration of rhein for 8 or 16 weeks in db/db mice significantly reduced fasting blood glucose (FBG) level and improved glucose tolerance. Cell apoptosis assay using both pancreatic sections and cultured pancreatic β-cells indicated that rhein strongly inhibited β-cell apoptosis. Morphological study showed that rhein was mainly localized at β-cell mitochondria and rhein could preserve mitochondrial ultrastructure by abolishing hyperglycemia-induced mitochondrial fission protein dynamin-related protein 1 (Drp1) expression. Western blot and functional analysis confirmed that rhein protected the pancreatic β-cells against hyperglycemia-induced apoptosis via suppressing mitochondrial Drp1 level. Finally, mechanistic study further suggested that decreased Drp1 level by rhein might be due to its effect on reducing cellular reactive oxygen species. Taken together, our study demonstrates for the first time that rhein can serve as a novel therapeutic agent for hyperglycemia treatment and rhein protects pancreatic β-cells from apoptosis by blocking the hyperglycemia-induced Drp1 expression.Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is an anthraquinone compound isolated from rhubarb that has been used for more than 2,000 years in China to treat constipation, gastrointestinal hemorrhage, and ulcers (1). In our previous work, we found that rhein could improve glucose metabolism disorders in diabetic mice, and its effect on reducing blood glucose level was even stronger than rosiglitazone and benazepril (2,3). Moreover, rhein also inhibited apoptosis of islet cells and protected islet function (4). Using mouse nonalcoholic fatty liver disease as an animal model associated with obesity, insulin resistance, and inflammatory disorders, Sheng et al. (5) reported that rhein could ameliorate fatty liver disease in diet-induced obese mice via negative energy balance, hepatic lipogenous regulation, and immunomodulation. Recent antihyperglycemic study by Chatterjee et al. (6) suggests that rhein, as well as other natural inhibitors such as aloins and capparisine, may be a foundation for a better antidiabetic therapy. However, the mechanism underlying these protective effects of rhein remains unclear.Increasing evidence suggests that β-cell failure is the mainstay of the pathogenesis of type 2 diabetes (7). Although the precise mechanisms underlying the β-cell dysfunction in type 2 diabetes are not fully understood, hyperglycemia has been shown as a major factor to cause the β-cell apoptosis. Once hyperglycemia develops, the pancreatic β-cell is exposed to increased metabolic flux and associated cellular stress, leading to impairment of β-cell function and survival, a process called glucotoxicity (8,9). In type 2 diabetes, hyperglycemia is commonly associated with deregulation of lipid metabolism and elevation of free fatty acids, which also contribute to β-cell dysfunction (8,10). Moreover, high levels of glucose can also amplify lipotoxicity (10). The thiazolidinedione peroxisome proliferator–activated receptor-γ activator drugs, rosiglitazone and pioglitazone, have been widely used to suppress insulin resistance in type 2 diabetic patients (11). Although rhein shows a similar or even better effect on reducing mouse blood glucose level than rosiglitazone, the underlying mechanism remains unclear. It has been known that mitochondrial fission and fusion modulators, dynamin-related protein 1 (Drp1) (12), optic atrophy protein 1 (Opa1) (13), prohibitin (14), and mitofusin (15), collectively control the dynamic balance of mitochondria fission and fusion processes and consequent mitochondria functions. Previous studies have demonstrated that Drp1 plays an important role in promoting hyperglycemia-induced apoptosis of β-cells and neurons (12,16,17). Drp1 expression was increased drastically in islet β-cells under hyperglycemia conditions. Estaquier and Arnoult (18) further demonstrated that inhibiting Drp1-mediated mitochondrial fission could selectively prevent the release of cytochrome c, a mediator of apoptosis, from mitochondria. In contrast to the mitochondria fission modulators, which are upregulated or activated by stress factors such as high concentration of glucose (HG), mitochondria fusion modulators are generally reduced when cells are challenged with proapoptotic insults. Recent studies by Kushnareva et al. (19) and Leboucher et al. (15) showed that stress-induced loss of Opa1 and mitofusin can facilitate mitochondrial fragmentation and cell apoptosis. However, it remains to be determined whether rhein executes its protective role in pancreatic β-cells through regulating the expression or activation of these mitochondria fission/fusion modulators.In the current study, we used db/db mice and a pancreatic β-cell line (NIT-1) to study the protective effect of rhein. Our results showed that rhein largely localized at mitochondria in the β-cells and that it strongly protected pancreatic β-cells from hyperglycemia-induced apoptosis through suppressing Drp1 activation and Drp1-mediated mitochondria fission.     

Complex anatomy surrounding the left atrial posterior wall: analysis with 3D computed tomography

Few studies have explored the topographic anatomy of the esophagus, posterior wall of the left atrium (LA), or fat pads using multidetector computed tomography (MDCT) to prevent the risk of esophageal injury during atrial fibrillation (AF) ablation. MDCT was performed in 110 consecutive patients with paroxysmal or persistent AF before the ablation procedure to understand the anatomic relationship of the esophagus. Two major types of esophagus routes were demonstrated. Leftward (type A) and rightward (type B) routes were found in 90 and 10% of the patients, respectively. A type A route had a larger mean size of the LA than type B. The fat pad was identifiable at the level of the inferior pulmonary vein in 91% of the patients without any predominance of either type. The thickness of the fat pad was thinner in the patients with a dilated LA (>42?mm) than in those with a normal LA size (??42?mm) (p?=?0.01). The results demonstrated that the majority of cases had a leftward route of the esophagus. There was a close association between the LA dilatation and fat pad thinning. With a dilated LA, the esophagus may become easily susceptible to direct thermal injury during AF ablation. Visualization of the anatomic relationship may contribute to the prevention of the potential risk of an esophageal injury.     

A prostacycline analog prevents chronic myocardial remodeling in murine cardiac allografts

ONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2 synthase inhibitory activity. We investigated the effect of ONO-1301MS on myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2(?bm12?) KhEg (a class II mismatch combination) to examine chronic rejection. ONO-1301MS did not prolong full allomismatch cardiac graft survival. Severe myocardial fibrosis with high collagen concentration was observed in untreated class II mismatch allografts on day 60. However, significantly suppressed myocardial fibrosis with less collagen synthesis was observed in the ONO-1301MS-treated group compared to the control group. ONO-1301MS could be an effective strategy to suppress chronic myocardial remodeling in cardiac transplantation.