Renal Artery Ligation Research Articles

A Preclinical Systematic Review of Curcumin for Protecting the Kidney with Ischemia Reperfusion Injury.

Renal ischemia-reperfusion injury (RIRI) refers to a phenomenon associated with dysfunction of the kidney and tissue damage. Unfortunately, no specific drugs have been found that effectively prevent and treat RIRI. Curcumin (Cur), a polyphenol extracted from turmeric, possesses a variety of biological activities involving antioxidation, inhibition of apoptosis, inhibition of inflammation, and reduction of lipid peroxidation. Eight frequently used databases were searched using prespecified search strategies. The CAMARADES 10-item quality checklist was used to evaluate the risk of bias of included studies, and the RevMan 5.3 software was used to analyze the data. The risk of bias score of included studies ranged from 3 to 6 with an average score of 5.22. Compared with the control group, Cur significantly alleviated renal pathology, reduced blood urea nitrogen and serum creatinine levels, and improved inflammatory indexes, oxidant, and apoptosis in RIRI animal models. Despite the heterogeneity of the response to Cur in terms of serum creatinine, BUN, TNF-alpha, and SOD, its effectiveness for improving the injury of RIRI was remarkable. In the mouse model subgroup of serum creatinine, the effect size of the method of unilateral renal artery ligation with contralateral nephrectomy and shorter ischemic time showed a greater effect than that of the control group. No difference was seen in the methods of model establishment, mode administration, or medication times. The preclinical systematic review provided preliminary evidence that Cur partially improved RIRI in animal models, probably via anti-inflammatory, antioxidant, antiapoptosis, and antifibrosis activities and via improving microperfusion. ARRIVE guidelines are recommended; blinding and sample size calculation should be focused on in future studies. These data suggest that Cur is a potential renoprotective candidate for further clinical trials of RIRI.

Induction of large cerebral aneurysms by intraperitoneal administration of β-aminopropionitrile fumarate in male rats.

It is necessary and useful to obtain an experimental model which steadily and rapidly induces aneurysms for investigation of the pathogenesis of cerebral aneurysm. We attempted to examine whether intraperitoneal administration of β-aminopropionitrile fumarate (BAPN-F) with additional treatments of induced hypertension and hemodynamic stress could steadily and rapidly induce aneurysms in male rats. Seven-week-old male Sprague-Dawley rats pretreated with ligation of left common carotid and bilateral posterior renal arteries were administrated BAPN-F intraperitoneally. Induction rate and size of aneurysms was investigated with varying dose and duration of BAPN-F administration (low dose; 400 mg/kg/week for 4 or 8 weeks and high dose; 2800 mg/kg/week for 8 or 12 weeks). Induction rate in the high-dose groups was significantly higher (P<0.01) than that in the low-dose groups. Making comparisons between 8 and 12 weeks of the high-dose groups, while there was no difference in induction rate (8 weeks; 85.2% vs. 12 weeks; 76.9%), aneurysmal size was larger in 12 weeks (8 weeks; 127.5 μm, vs. 12 weeks; 181.7 μm in terms of median) but lethal intrathoracic hemorrhage was increased in 12 weeks (8 weeks; 7.4% vs. 12 weeks; 30.8%). Induction rate of large aneurysm was 22.2% and 30.8% in 8 and 12 weeks of the high-dose groups, respectively. High-dose BAPN-F administration can cause high-frequency aneurysmal induction. Although there was the difference in size and mortality rate based on administration duration, intraperitoneal administration of 2800 mg/kg/week BAPN-F for 8 weeks would be suitable for aneurysmal induction.

Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P&lt;0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P&lt;0.01 or P&lt;0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P&lt;0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P&lt;0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P&lt;0.01 or P&lt;0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

Arginyltransferase knockdown attenuates cardiac hypertrophy and fibrosis through TAK1-JNK1/2 pathway

Myocardial hypertrophy, an inflammatory condition of cardiac muscles is a maladaptive response of the heart to biomechanical stress, hemodynamic or neurohormonal stimuli. Previous studies indicated that knockout of Arginyltransferase (ATE1) gene in mice and embryos leads to contractile dysfunction, defective cardiovascular development, and impaired angiogenesis. Here we found that in adult rat model, downregulation of ATE1 mitigates cardiac hypertrophic, cardiac fibrosis as well as apoptosis responses in the presence of cardiac stress i.e. renal artery ligation. On contrary, in wild type cells responding to renal artery ligation, there is an increase of cellular ATE1 protein level. Further, we have shown the cardioprotective role of ATE1 silencing is mediated by the interruption of TAK1 activity-dependent JNK1/2 signaling pathway. We propose that ATE1 knockdown in presence of cardiac stress performs a cardioprotective action and the inhibition of its activity may provide a novel approach for the treatment of cardiac hypertrophy.

MicroRNA-331-3p maintains the contractile type of vascular smooth muscle cells by regulating TNF-α and CD14 in intracranial aneurysm

Dysfunction of vascular smooth muscle cells (VSMCs) may be linked to intracranial aneurysm (IA) formation. VSMCs possess a phenotypic plasticity, capable of changing from a mature, contractile to a less differentiated, synthetic phenotype. In this study, we identify a microRNA candidate miR-331-3p that participates in regulating differentiation properties of VSMCs. The expression of TNF-α and CD14 was quantified in IA wall tissues obtained from 96 IA patients and their associations with clinicopathological features of IA were assessed. Then the interactions between miR-331-3p, TNF-α and CD14 were evaluated by determination of luciferase activity. Differentiated properties of VSMCs were assessed from phenotypic markers of contractile VSMCs, a-SMA and E-cadherin, and of synthetic VSMCs, ICAM-1, MCP-1, IL-6, MMP-2 and MMP-9. Rat IA models by ligation of left carotid artery and left renal artery and histological analysis of induced IAs were performed. The TNF-α and CD14 was highly expressed in IA wall tissues and associated with the type and diameter of aneurysm. Depletion of TNF-α or CD14 retarded VSMC apoptosis and transformation to the synthetic type but facilitated cell proliferation. Elevations in miR-331-3p, a direct negative regulator of both TNF-α and CD14, also reduced VSMC apoptosis and prevented VSMCs from synthetic type and increase their proliferation. Furthermore, miR-331-3p was demonstrated to inhibit the formation of IA by down-regulating TNF-α and CD14 in vivo. In conclusion, miR-331-3p maintains the contractile type of VSMCs, thus possibly inhibiting the progression of IA. These findings provide potential new strategies for the clinical treatment of IA.

Dexmedetomidine hydrochloride up-regulates expression of hypoxia inducible factor-1α to alleviate renal ischemiareperfusion injury in diabetic rats

To verify whether dexmedetomidine hydrochloride (Dex) alleviates renal ischemia-reperfusion (IR) injury in diabetic rats by increasing the expression of hypoxia inducible factor-1α (HIF-1α). A rat model of type 2 diabetes mellitus was established by high-fat diet and streptozotocin injection. The rats were subjected to daily intragastric administration of 0.05 mg/kg digoxin for 7 consecutive days and intraperitoneal injection of Dex 2 h before renal IR injury induced by ligation of the bilateral renal arteries for 60 min followed by reperfusion for 120 min. After reperfusion, blood samples were taken for detection of serum creatinine (Scr) and urea nitrogen (BUN) levels. Western blotting was used to detect the expression of HIF-1α, cleaved caspase-3, Bcl-2, and Bax in the renal tissues; the expression of the HIF-1α, p-eNOS, and eNOS were detected using ELISA. The percentage of apoptotic glomerular cells was assessed using TUNEL assay. The levels of Scr, BUN, HIF-1α, p-eNOS, and eNOS and the percentage of apoptotic cells in both normal and diabetic rats increased significantly after renal IR injury (P &lt; 0.05). The expressions of Scr, BUN, p-eNOS, and eNOS decreased while HIF-1α expression increased significantly in Dex-treated rats with renal IR injury (P &lt; 0.05). Compared with the non-diabetic rats, the diabetic rats showed more obvious increase in the expressions of Scr, BUN, p-eNOS, and eNOS following renal IR injury. In the diabetic rats with renal IR injury, Dex treatment prior to the injury significantly lowered the expressions of Scr, BUN, p-eNOS, eNOS, cleaved caspase-3, and Bax, decreased the percentage of apoptotic cells, and increased the levels of HIF-1a and Bcl-2 (P &lt; 0.05). Digoxin treatment significantly antagonized the effects of Dex in the diabetic rats with renal IR injury by increasing the expressions of cleaved caspase-3 and Bax, promoting glomerular cell apoptosis, and decreasing renal expressions of HIF-1 and Bcl-2 (P &lt; 0.05). Dex alleviates renal IR injury in diabetic rats probably by inhibiting renal expression of HIF-1α and glomerular cell apoptosis.

Renal Hilus Ligation With Single Stapler in Laparoscopic Donor Nephrectomy

BackgroundLigation of renal hilus is the most important stage of laparoscopic donor nephrectomy. Laparoscopic staplers are securely used for renal pedicle control. We present our donor nephrectomy cases in which we used 1 stapler for renal artery and vein ligation. MethodsDemographic data, number of arteries and veins, ligation types, operation time, and complication rates are recorded. ResultsOne hundred twenty laparoscopic donor nephrectomy cases who were operated between December 2017 and August 2018 in İstinye University Hospital and İstanbul Aydın University Hospital were retrospectively evaluated. All of the operations were done by 2 surgeons with a fully laparoscopic method. None of the cases were converted to open nephrectomy. There was 1 renal artery in 110 (91.7%) cases, 2 renal arteries in 9 (7.5%) cases, and 3 arteries in 1 (0.8%) case. Renal artery and vein were ligated with single stapler in 115 (95.8%) cases. Double stapler was used in 5 (4.2%) patients. There were no major complications for donors and no implantation problems for grafts. DiscussionLaparoscopic donor nephrectomy is the most used technique for living donor operations. Vascular stapler is securely used for renal artery and vein ligation with high costs. Two or, due to the number of vessels, sometimes 3 staplers are used in the standard technique. In our study, the operation was finished securely in 95.8% of the patients with single stapler use. Single stapler use for ligating renal hilus is safe in kidneys even with suitable multiple arteries and veins in laparoscopic donor nephrectomy.

En bloc removal of a large leiomyosarcoma arising from the inferior vena cava using retroperitoneal laparoscopic dissection of posterior vessels followed by cavectomy in a thoracoabdominal approach

A 55-year-old Japanese woman had a large retroperitoneal tumor involving the inferior vena cava (IVC) in the right infrahepatic space. We performed en bloc tumor resection with the right kidney and ipsilateral adrenal gland. Because of the large tumor size, we used a retroperitoneal laparoscopic approach for the posterior dissection and performed renal artery ligation. Following open conversion by a thoracoabdominal anterior approach, the tumor was completely removed without major reconstruction. Pathological examination confirmed a leiomyosarcoma arising from the IVC. Retroperitoneal laparoscopic dissection of the posterior side enabled easy and safe surgery even for a large tumor involving the IVC.

Renovascular Hypertension Aggravates Atherosclerosis in Cholesterol-Fed Rabbits

Background: Hypertension is a major risk factor for atherosclerotic disease. However, it is still not clear whether mechanical stress caused by hypertension directly affects the atherosclerotic development in the aorta and coronary arteries. Objectives and Methods: We generated a hypertensive (HTN) rabbit model by surgical removal of the left kidney and partial ligation of the right renal artery. After a 16-week cholesterol diet, we compared aortic and coronary atherosclerosis of HTN rabbits with those of normotensive rabbits. Results: Hypertension did not affect lipid and apolipoprotein levels in plasma but led to a 3.0-fold increase in aortic atherosclerosis and a 1.7-fold increase in coronary atherosclerosis compared with control rabbits. Enhanced atherosclerosis in HTN rabbits was caused by significant increases in macrophages and smooth muscle cells in the lesions. Furthermore, oxidized LDL contents in the lesions were significantly increased in HTN rabbits. In addition, HTN rabbits exhibited prominent hyaline arteriolosclerosis in coronary arterioles. Conclusions: These results indicate that hyper tension not only enhances atherosclerosis in large arteries including the aorta and coronary arteries but also affects hyaline arteriolosclerosis in small arteries.

Study on acute kidney injury model induced by renal ischemia-reperfusion in rats

In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 μmol·L-1 to more than 430 μmol·L-1. Among them,5 rats showed less than 100 μmol·L-1 serum Crea,20 rats with 100-200 μmol·L-1 serum Crea and 12 rats with more than 430 μmol·L-1. Rats with serum Crea between 300-430 μmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 μmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 μmol·L-1 and the group of Crea 300-370 μmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 μmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.

A4020 Reduction of Blood Pressure Immediately After Renal Artery Adventitia Stripping During Total Nephroureterectomy

Objectives: Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. Methods: When the renal artery adventitia was stripped and cauterized just before renal artery ligation, hemodynamic monitoring revealed a gradual decrease of blood pressure in both patients. Results: This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. Conclusion: A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective.

Open repair of ruptured abdominal aortic aneurysm with associated horseshoe kidney.

Ruptured abdominal aortic aneurysms (RAAA) with concomitant horseshoe kidney (HK) present a unique challenge at the time of repair. The aim of this article was to propose the most rationale strategy during open repair (OR) of RAAA in the presence of HK. We identified and analyzed all patients treated at the clinic due to RAAA and HK. An extensive search was performed on all articles published up to August of 2017 describing open and endovascular repair of RAAA with concomitant horseshoe kidney. The following data were extracted and analyzed: patient number, number of renal arteries, Crawford classification of horseshoe kidney vascularization, type of aortic reconstruction, management with renal arteries, 30-day kidney failure and outcome. Transperitoneal approach followed by supraceliac aortic cross clamping without the division of the renal isthmus occurred in all our six cases. Four of them required additional procedures with accessory renal arteries after aortic replacement. Three of patients (50%) died during the first 30 postoperative days, while one developed transitory renal insufficiency. The renal isthmus was preserved in 43.90% and divided in 46.34% of cases. Crawford type I of HK vascularization was presented in 21.95% of cases, type II also in 39.02%, while the type III in 19.51% of cases. In 46.33% of cases a procedure with renal arteries was necessary. In 26.82% accessory renal arteries were ligated, while in 19.51% preserved (reattachment or aorto-renal bypass). Thirty-day mortality was 21.95%, while the incidence of postoperative renal failure was also 21.95%. There was not significant correlation between the renal artery ligation and the postoperative renal failure (r=-0.81, P=0.59). Transperitoneal approach should be preferred during urgent OR of RAAA with concomitant HK. A supraceliac aortic cross clamping and the placement of occlusive Fogarty catheters into both iliac arteries are recommended for proximal and distal bleeding control. Preservation of accessory renal arteries that are larger than 3 mm in diameter or supply more than 30% of renal parenchima is recommended. The division of the renal isthmus should be avoided if vascularized. It seems that renal arteries could be covered in emergency EVAR without any implications on postoperative kidney function, allowing broader aplication of endovascular treatment for thesse patients.

Hypertension Enhances Advanced Atherosclerosis and Induces Cardiac Death in Watanabe Heritable Hyperlipidemic Rabbits

Hypertension is a major risk factor for the development of atherosclerosis. Cardiovascular risk has been reported to be significantly increased in hyperlipidemic patients with hypertension. However, it is not clear whether hypertension can directly destabilize plaques, thereby enhancing cardiovascular events. To examine whether hypertension enhances the development of atherosclerosis and increases plaque vulnerability, we generated hypertensive Watanabe heritable hyperlipidemic (WHHL) rabbits by surgical removal of one kidney and partial ligation of the other renal artery and compared the nature of aortic and coronary atherosclerosis in hypertensive WHHL rabbits with normotensive WHHL rabbits. All hypertensive WHHL rabbits died from 34 to 56 weeks after surgery, whereas no normotensive WHHL rabbits died. Pathologic examinations revealed that hypertensive WHHL rabbits showed different degrees of myocardial infarction caused by severe coronary stenosis along with myocardial hypertrophy. Furthermore, aortic lesions in hypertensive WHHL rabbits exhibited a higher frequency of intraplaque hemorrhage and vulnerable plaques than those in normotensive WHHL rabbits. These results indicate that hypertension induced by the surgical removal of one kidney and partial ligation of the other renal artery method in WHHL rabbits may not only enhance the development of atherosclerosis but also destabilize the plaques, increasing cardiac death.

Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats.

Orellanine is a nephrotoxin found in mushrooms of the Cortinarius family. Accidental intake of this substance may cause renal failure. Orellanine is specific for proximal tubular cells and could, therefore, potentially be used as treatment for metastatic renal cancer, which originates from these cells. However, more information is needed about the distribution and elimination of orellanine from the body to understand its potential use for therapy. In this study, 5 mg/kg orellanine (unlabeled and 3H-labeled) was injected intravenously in rats (Wistar and Sprague Dawley). Distribution was measured (Wistar rats, n = 10, n = 12) using radioluminography and the highest amount of orellanine was found in the kidney cortex and bladder at all time-points investigated. The pharmacokinetic properties of orellanine were investigated using LC-MS/MS and β-scintillation to measure the amount of orellanine in plasma. Three groups of rats were investigated: control rats with intact kidneys (n = 10) and two groups with bilateral renal artery ligation (n = 7) where animals in one of these groups were treated with peritoneal dialysis (n = 8). Using LC-MS/MS, the half-life of orellanine was found to be 109 ± 6 min in the controls. In the groups with ligated renal arteries, orellanine had a half-life of 756 ± 98 min without and 238 ± 28 min with dialysis. Thus, orellanine was almost exclusively eliminated by glomerular filtration as well as by peritoneal dialysis.

Safety of Polymer Clips in Laparoscopic Living Donor Nephrectomy: Indonesian Experience

To assess the reliability and safety of polymer clips for vascular control in laparoscopic living donor nephrectomy. We collected data retrospectively from all laparoscopic living donor nephrectomy performed in Ciptomangunkusumo Hospital, Jakarta, Indonesia. Polymer clips was applied for both renal artery and renal vein ligation. The incidence of polymer clip failure was recorded accordingly. Between November 2011 and August 2015, we evaluated 260 patients of laparoscopic living donor nephrectomy in a center. The left kidney was harvested from 219 (84.5%) patients. Multiple renal arteries was discovered in 25 (9.6%) patients. For all cases we used polymer clips to control the renal artery (XL and L) and renal vein (XL). We placed 2 clips as proximal as possible to the aorta or caval vein. The median estimated blood loss was 100 (20–2000) ml. A blood loss of 2000 ml occurred in one/case of clip dislodgement. The median time to clip (the length of time from first incision to renal artery clamping) was 155 (68–318) minutes. The median warm ischemic time (the length of time from clamping to cold ischemic time) was 3.01 (1.22–30.43) minutes. There were 10 cases with warm ischemic time of more than 10 minutes. Three cases (1.2%) of clip failures occurred. One patient needed conversion to open surgery to achieve adequate vascular control. Two patients experienced improper locking of the polymer clips, necessitating clips reapplication. The use of polymer clips for vascular control in laparoscopic living donor nephrectomy is reliable and safe when properly applied. However the evaluation of renal vascular stump after harvesting donor kidney is an important step to ensure the right placement and safety of polymer clips.

Atorvastatin Inhibits Inflammatory Response, Attenuates Lipid Deposition, and Improves the Stability of Vulnerable Atherosclerotic Plaques by Modulating Autophagy.

Atherosclerosis is a chronic disease comprising intima malfunction and arterial inflammation. Recent studies have demonstrated that autophagy could inhibit inflammatory response in atherosclerosis and exert subsequent atheroprotective effects. Our previous study also demonstrated the role of autophagy in the inhibition of inflammation by atorvastatin in vitro. Therefore, in the present study, we aimed to determine whether atorvastatin could upregulate autophagy to inhibit inflammatory cytokines secretion, lipid accumulation, and improve vulnerable plaque stability, both in vitro and in vivo. First, we established a vulnerable atherosclerotic plaque mouse model through partial ligation of left common carotid artery and left renal artery to explore the effect of atorvastatin on vulnerable plaques. The results showed that atorvastatin could enhance the stability of vulnerable atherosclerotic plaques and reduce the lesion area in the aorta. Atorvastatin could also inhibit NLRP3 inflammasome activation and inflammatory cytokines, such as IL-1β, TNF-α, and IL-18 secretion in vivo. Atorvastatin treatment upregulated the expression of autophagy-related protein microtubule-associated protein light chain (LC3B) and downregulated the expression of SQSTM1/p62, which suggested that autophagy was activated in vulnerable plaques. Transmission electron microscopy further demonstrated the atorvastatin-induced increase in autophagy activity in vulnerable atherosclerotic plaques. We employed oxidized low-density lipoprotein (ox-LDL) to stimulate RAW264.7 cells with atorvastatin, which showed that atorvastatin could attenuate lipid deposition, ameliorate inflammation, inhibit NLRP3 inflammasome activation, and enhance autophagy in vitro. All these beneficial effects were abolished by 3-methyladenine treatment, an autophagy inhibitor. Atorvastatin also significantly inhibited the phosphorylation of mTOR, which strongly suggested the involvement of the mTOR pathway. Our study proposed a new role for atorvastatin as an autophagy inducer to exert anti-inflammatory and atheroprotective effects, to stabilize vulnerable atherosclerotic plaques.

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy.

Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy". We describe here an experimental CKD mouse model, named 5/6th partial nephrectomy (PNx) with pole ligation, which developed uremic cardiomyopathy at four weeks post-surgery. This PNx model was performed by a two-step surgery. In step-one surgery, both poles of the left kidney were ligated. In step-two surgery, which was performed 7 days after the step-one surgery, the right kidney was removed. For the sham surgery, the same surgery procedures were performed but without pole ligation of the left kidney or removal of the right kidney. The surgical procedures are easier and less time-consuming, compared to other methods. However, the remnant functional renal mass is not as easily controlled as the renal artery ligation. Four weeks after surgery, in comparison with the sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.

A Mouse 5/6&lt;sup&gt;th&lt;/sup&gt; Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy". We describe here an experimental CKD mouse model, named 5/6th partial nephrectomy (PNx) with pole ligation, which developed uremic cardiomyopathy at four weeks post-surgery. This PNx model was performed by a two-step surgery. In step-one surgery, both poles of the left kidney were ligated. In step-two surgery, which was performed 7 days after the step-one surgery, the right kidney was removed. For the sham surgery, the same surgery procedures were performed but without pole ligation of the left kidney or removal of the right kidney. The surgical procedures are easier and less time-consuming, compared to other methods. However, the remnant functional renal mass is not as easily controlled as the renal artery ligation. Four weeks after surgery, in comparison with the sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.

Abstract 106: microRNA-33a Regulates Myocardin Expression and Attenuates Cardiac Remodeling in Renal Artery Ligation Model of Heart Failure

Myocardin (MYOCD), a cardiac specific transcriptional co-activator is up-regulated in heart failure (HF). Up-regulation of MYOCD expression has been proposed to be an important adaptive response in cardiac remodelling. However, molecular mechanisms contributing to increased cardiac MYOCD expression in HF are not known. The goal of this study was to identify microRNA(s) regulating cardiac MYOCD expression and to study the effect of cardiac modulation of MYOCD specific miRNA in an animal model of HF. miRNA(s) targeting MYOCD were identified using in silico approach and validated by 3’-UTR luciferase reporter assay. Cardiac expression of miRNA was measured in endomyocardial biopsies from idiopathic DCM (IDCM) patients, renal artery ligation rat model of HF (RAL) and in Ang II treated cardiomyocytes by real-time PCR. miRNA-33a, miRNA-33b, miRNA-139 and miRNA-542 were identified with MYOCD as putative target. Cardiac expression of miRNA-33a and miRNA-33b was significantly decreased, whereas expression of miRNA-139 and miRNA-542 was not altered in IDCM. miRNA-33a expression was also decreased in RAL and in Ang II treated cardiomyocytes. Luciferase assay confirmed MYOCD as target gene for miRNA-33a. miRNA-33a overexpression significantly decreased expression of MYOCD, ANP and fibrotic genes in Ang II treated cardiomyocytes. Cardiac specific delivery of miRNA-33a, using a homing peptide conjugated siRNA, attenuated cardiac hypertrophy and fibrosis, decreased expression of ANP, β-MHC and fibrotic genes and ameliorated the impaired diastolic dysfunction in RAL. Our results provide the first evidence that miRNA-33a regulates MYOCD expression and cardiac specific augmentation of miRNA-33a attenuated cardiac remodelling and partially restored left ventricular function. Our results suggest miR-33a as a potential therapeutic target in reversal of cardiac remodelling and improvement in heart function in HF.

Surgical intervention for renal cell carcinoma with inferior vena cava extension combined with laparoscopic procedure.

Clear cell renal cell carcinoma (ccRCC) shows extreme hypervascularity, which may cause significant bleeding during surgery. For this reason, control of arterial blood supply is an important factor in the choice of operative procedure and in avoiding perioperative complications. This case series reports the successful dissection of renal artery in the preliminary stage of laparoscopic procedure in three ccRCC patients with inferior vena cava (IVC) extension. Patient 1 had right renal cell carcinoma (RCC) with level I tumor thrombus through two renal veins, and the renal artery was successfully dissected by retroperitonealscopic approach. Patient 2 had right invasive, immobilized RCC with significant infiltration to IVC and liver. Ligation of renal artery was performed by transperitoneal laparoscopic procedure. Patient 3 had left RCC with level III tumor thrombus and lung metastasis. Ligation of left renal artery and mobilization of peritoneal organs and kidney were performed by transperitoneal laparoscopic surgery. These cases suggest that combined laparoscopic-open surgery for RCC with IVC extension may facilitate early control of arterial blood supply.