Vascular Complications In Patients Research Articles

Relationship between vitamin D status and vascular complications in patients with type 2 diabetes mellitus

We aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) and microvascular complications in type 2 diabetes mellitus (T2DM) patients. It was hypothesized that lower 25(OH)D would be associated with increased microvascular complications in T2DM. A total of 257 T2DM patients (111 men, 146 women) who underwent diabetic microvascular complication (peripheral neuropathy, nephropathy, retinopathy) studies were recruited. Patients were categorized into 3 groups according to vitamin D status: vitamin D sufficient (n = 41, 25[OH]D ≥ 20 ng/mL), vitamin D insufficient (n = 132, 10 ≤ 25[OH]D < 20 ng/mL), and vitamin D deficient (n = 84, 25[OH]D < 10 ng/mL). In men, the prevalence of diabetic peripheral neuropathy (DPN) was significantly higher in patients with vitamin D deficiency than in those with insufficiency or sufficiency (38%, 11.7%, and 10%, respectively; P = .005). In addition, the prevalence of diabetic nephropathy (DN) was significantly higher in women with vitamin D deficiency than in the other 2 groups (40%, 20.6%, and 0%; P = .007). Compared with men in the vitamin D–sufficient group (reference), men in the vitamin D–deficient group had an increased risk of DPN after adjusting for confounding factors (odds ratio, 7.79; 95% confidence interval, 1.52-40.05). For women, when the vitamin D–sufficient group was used as a reference, those in the vitamin D–deficient group had an increased risk of DN after adjusting for confounding factors (odds ratio, 4.27; 95% confidence interval, 1.58-11.56). This present study found that a serum 25(OH)D level less than 10 ng/mL is independently associated with increased DPN in male patients and increased DN in female patients with T2DM.

Results of the ADVANCE trial and interventional observational program ADVANCE-ON: whether our understanding of the relationship of glycemic factors and the risk of vascular complications in patients with type 2 diabetes has changed?

The results from the analysis of the ADVANCE trial and post-intervention program ADVANCE-ON are presented in this article. These studies are dedicated to study the effect of intensive glycemic control on the incidence of micro- and macrovascular events in patients with type 2 diabetes mellitus and evaluation of long-term results of intensive glycemic control. We discuss the progress of views on the impact of glycemic control on the development of cardiovascular complications. According to the analysis of the research results, gliclazide MR is safe in patients with type 2 diabetes at high risk for cardiovascular complications.

Pin1 inhibitor Juglone prevents diabetic vascular dysfunction

BackgroundAtherosclerosis is a major cause of mortality in patients with diabetes. However, novel breakthrough therapies have yet to be approved in this setting. Prolyl-isomerase-1 (Pin1) is emerging as a key molecule implicated in vascular oxidative stress and inflammation. In the present study, we investigate whether pharmacological inhibition of Pin1 may protect against diabetes-induced oxidative stress, endothelial dysfunction and vascular inflammation. Methods and ResultsExperiments were performed in human aortic endothelial cells (HAECs) exposed to normal (5mmol/L) or high glucose (25mmol/L) concentrations, in the presence of Pin1 inhibitor Juglone (10μM) or vehicle (<1% ethanol). In parallel, streptozotocin-induced diabetic mice were treated with Juglone i.p. every other day for 30days (1mg/Kg). Organ chamber experiments were performed in aortic rings to assess endothelium-dependent relaxations to acetylcholine (Ach 10−9 to 10−6mol/L). Mitochondrial oxidative stress, organelle integrity as well as NF-kB-dependent inflammatory signatures were determined both in HAECs and aortas from diabetic mice. In HAECs, ambient hyperglycemia increased mitochondrial superoxide anion generation while treatment with Juglone prevented this phenomenon. Pharmacological inhibition of Pin1 also preserved mitochondrial integrity, nitric oxide availability and endothelial expression of adhesion molecules. Interestingly enough, endothelial dysfunction, oxidative stress and NF-kB-driven inflammation were significantly attenuated in diabetic mice chronically treated with Juglone as compared to vehicle-treated animals. ConclusionPharmacological inhibition of Pin1 by Juglone prevents hyperglycemia-induced vascular dysfunction. Taken together, our findings may set the stage for novel therapeutic approaches to prevent vascular complications in patients with diabetes.

Risk factors for vascular access-related complications in patients undergoing early invasive strategy

ABSTRACT Background The knowledge of risk factors related to vascular access complications in patients undergoing early invasive strategy allows the adoption of methods to minimize them. Methods We performed a subanalysis of the ARISE study, aiming to identify predictors of vascular complications in patients randomized to the radial or femoral techniques with the use of vascular closure device (VCD). Results A total of 240 patients with a mean age of 63.0 ± 10.7 years were included, with 30.8% of diabetics. Except for a higher prevalence of women in the radial group, there were no clinical differences between the groups. Percutaneous coronary intervention was performed in 86.7% of the cases. The rate of vascular complications after 30 days was 13.3% in the radial group, due to hematoma > 5 cm (6.7%) and asymptomatic artery occlusion (5.8%), and 12.5% in femoral group, due to hematoma > 5 cm, without significant difference. The following were identified as risk factors for vascular access complications: body mass index (BMI), previous stroke, longer duration of the procedure, and VCD failure. At the stratified analysis, female gender and high or very high-risk CRUSADE score were predictors of complications only for the femoral group. In the multivariate model, the factors that remained significant were BMI and VCD failure. Conclusions The radial and femoral techniques, with the use of VCD, shared variables that were predictors of complications. Risk factors, such as female gender and high-risk CRUSADE score, were attenuated by the use of the radial technique.

The impact of TAVI on vascular complications incidence: a literature review

Aim: This article provides a literature review on the post-procedural outcomes of patients who have undergone transfemoral transcatheter aortic valve implantation (TAVI). Background: TAVI is a less invasive treatment option than surgical aortic valve replacement (SAVR) for aortic stenosis. Aortic stenosis in the UK has a prevalence rate of 5% in people aged 75 and over. Access sites used for TAVI procedures include trans-aortic, subclavian, carotid, apical (TA) and femoral (TF) ( National Institute for Health and Care Excellence (NICE), 2012 ). Transfemoral TAVI access sites were previously closed using an open surgical access technique (closure of the skin using sutures). However, over the years, the use of percutaneous access closure devices such as Perclose Proglide has increased. Nevertheless, there is a gap in the literature that assesses the postoperative vascular complications in patients who undergo TAVI. Conclusion: This review highlights the importance of measuring patients' post-procedural outcomes, as well as the need for increased confidence and competence in all health professionals in their provision of care to patients, and more evidence-based care. Relevance to clinical practice: Nurses can improve patient care by observing the patient and ensuring their safety following the TAVI procedure. They should therefore be competent in recognising any major or minor vascular complications after transfemoral TAVI and assessing their significance.

Uremic Toxicity of Advanced Glycation End Products in CKD.

Advanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product-specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD.

The clinical significance of the detection of serum hs-CRP and interleukin-17 in senium type 2 diabetes with macroangiopathy

Objective To explore the relationship between serum hs-CRP,IL-17 levels and senium type 2 diabetic macrovascular complications and its clinical significance. Methods The serum levels of hs-CRP and IL-17 were measured with immunoturbidimetry and ELISA respectively in 80 cases of type 2 diabetic patients with macrovascular complications,80 cases of the absence of any major vascular complications in patients with type 2 diabetes and 80 healthy subjects as the control. Results The serum hs-CRP and IL-17 levels of senium type 2 diabetic Patients with macrovascular complications were significantly higher than those of patients without macrovascular complication and healthy control group(t=19.18,23.14,all P 0.05); In patients of type 2 diabetic Patients with macrovascular complications,hs-CRP was positively correlated with serum IL-17(r=0.712,P<0.05). Conclusion Hs-CRP and IL-17might be involved in the process of inflammatory response to diabetic macroangiopathy, and may have important role in the pathogenesis of senium type 2 diabetic patients with macrovascular complications. Detemination of hs-CRP and IL-17 levels in type 2 diabetic patients may be useful for early detecting diabetic macrovascular complications and serve as the index in monitoring the state of diabetic macrovascular complications. Key words: Diabetes mellitus, type 2; Diabetic Angiopathies; Interleukin-17; C-Reactive Protein; Aged

Lung perfusion imaging in hepatopulmonary syndrome using 99mTc macroaggregated albumin

Hepatopulmonary syndrome is a serious pulmonary vascular complication in patients with chronic liver disease. It constitutes a triad of chronic liver disease, increased alveolar-arterial oxygen gradient, and evidence of intrapulmonary shunt (IPS). The diagnosis of IPS can be made by bubble echocardiography, technetium-99m-labeled macroaggregated albumin (99mTc-MAA) scintigraphy or pulmonary arteriography. Though echocardiography is a sensitive screening test, MAA scintigraphy can also quantify the extent of shunting.

Virtual 5-French intra-aortic pumping using a Glidesheath Slender and 6-French intra-aortic balloon catheter.

The aim of this study was to evaluate the feasibility and safety of the 6-Fr Glidesheath Slender, which has equivalent outer size to the conventional 5-Fr sheath, for use with the 6-Fr intra-aortic balloon pump (IABP) catheter. Between May 2014 and March 2015, 24 patients with acute coronary syndrome underwent percutaneous coronary intervention using a 6-Fr IABP catheter through a 6-Fr Glidesheath Slender for support. The adverse events, including access site complications, kinking of the sheath during the procedure, and any evidence of balloon pump failure, were retrospectively investigated. Insertion of the IABP catheter through either the femoral or brachial artery was successful in all patients. The mean support time was 32.4±22.0h. No major hemorrhagic event or severe limb ischemia was observed. Kinking of the shaft occurred during insertion in one patient; however, the subsequent balloon pumping was well maintained and did not require exchange of the sheath or IABP catheter. No kind of IABP failure was observed. Although this sheath was originally designed to allow radial access, our results suggest that the use of the Glidesheath Slender is feasible for insertion of the 6-Fr IABP catheter through the brachial and femoral arteries, and may reduce vascular complications in patients who undergo percutaneous coronary intervention.

Comparison of Angioseal and Manual Compression in Patients Undergoing Transfemoral Coronary and Peripheral Vascular Interventional Procedures.

Vascular closure devices (VCDs) were introduced in the early 1990s with the goal of limiting the time, labor, bed rest, and patient discomfort associated with manual compression (MC) for hemostasis after cardiovascular interventions. However, its advantage over MC has not been extensively studied after interventional procedures. The aim of this study was to do prospective, randomized study comparing the safety and efficacy of the Angio-Seal (AS) to that of MC in patients undergoing transfemoral coronary and peripheral vascular interventional procedure. A prospective, randomized trial was undertaken on consecutive series of patients admitted to King Fahd Hospital of the University for transfemoral coronary and peripheral vascular interventional procedures over 1 year. The study was designed to compare the hemostasis time in minutes and the incidence of vascular complications in patients receiving AS with those undergoing MC. All patients were on antiplatelets and received heparin during the procedure. During the study period, 160 patients were included, 80 in each group. There was a significant difference in mean time to hemostasis in minutes (15.83 ± 1.63 minutes for MC and 0.42 ± 0.04 minutes for the AS; p < 0.001), time to ambulation in minutes (280 ± 15 for MC and 120 for AS; p = 0.04) and in minor complications (33.8% in MC vs. AS 5%; p < 0.001). However, the major complication rate did not significantly differ between the two groups (0% in AS vs. 2.5% in MC; p = 0.15). AS was found to achieve rapid closure of the femoral access site safely in patients undergoing coronary and peripheral vascular interventional procedures under antiplatelets and systemic heparinization.

Home Blood Pressure Measurement in the Morning Related to Cancer in Patients with Type 2 Diabetes Mellitus: 10 Years-Term Results of a Longitudinal Study and Cancer

Previous longitudinal studies have demonstrated that blood pressure measurements at home (HBP) in the wakening- up display stronger predictive power for death, and vascular complications in patients with type 2 diabetes mellitus (T2DM) than clinic blood pressure measurements (CBP). The leading cause of death was cancer. Patients with T2DM have associated with cancer, and high CBP is a risk factor for cancer. Therefore, this study investigated whether HBP or CBP is related to cancer event in patients with T2DM for 10 years. At baseline, 400 Japanese patients with T2DM were classified as hypertensive (HT) or normotensive (NT) based on HBP and CBP. Mean (± SD) duration was 95 ± 35 months. Primary and secondary endpoints were death and cancer, respectively. Differences in outcome between HT and NT were analyzed using survival curves from Kaplan-Meier analysis and log-rank testing. Associated risk factors were assessed using Cox proportional hazards. On basis of HBP, death and event of cancer were significantly higher in HT than in NT. The leading cause of death was cancer. On basis of CBP, there was no significant difference in the incidence of death and event of cancer between patients with HT and NT at baseline. Associated risk factor for cancer was T2DM. Home morning HT may be reflected more keenly state of cancer than clinic HT, which may be superior to clinic NT. When we meet with such patients, it is important that cancer may be one of many causes for morning HT in Japanese patients with T2DM.

Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: the EURODIAB Prospective Complications Study

BackgroundImpaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, −2, −3, −9, −10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED).Methods493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, −2, −3, −9, −10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED.ResultsPatients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED.ConclusionsThese data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0195-2) contains supplementary material, which is available to authorized users.

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target.

ObjectivesIncreased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association.MethodsThis is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected.ResultsPatients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively).ConclusionsThe elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.

Subclinical hypothyroidism and the associations with macrovascular complications and chronic kidney disease in patients with Type 2 diabetes.

The prevalence of subclinical hypothyroidism (SCH) is high among patients with diabetes, although the relationship between SCH and diabetic vascular complications is unknown. This study aimed to determine the relationship between SCH and vascular complications in patients with Type2 diabetes. In this cross sectional study, 991 patients with Type2 diabetes were screened for thyroid function at their admission to the Second Affiliated Hospital of Chongqing Medical University. We compared the prevalence of coronary heart disease (CHD), ischaemic stroke and chronic kidney disease (CKD) with the prevalence of euthyroidism and SCH. Among the 991 patients, 126 (12.7%) patients had SCH. The prevalence of CHD was significantly higher in the SCH group than in the euthyroid group (22.2% and 15.0%, respectively; P=0.039). In the logistic regression analyses, SCH was associated with CHD [odds ratio (OR): 1.993; 95% confidence interval (CI): 1.135-3.497; P=0.016]. This association was stronger in patients aged ≥65years than in younger patients [2.474 (1.173-5.220); P=0.017]. No significant association was found between SCH and ischaemic stroke. Patients with severe SCH had a high risk of CKD [1.842 (1.120-3.029); P=0.016]. This study provides evidence that SCH in patients with Type2 diabetes is associated with a high prevalence of CHD (and CKD in severe SCH), although not with ischaemic stroke.

Nonsynonymous T280M gene variant of CX3CR1 in South Indian population is associated with reduced risk for vascular disease in patients with diabetes mellitus

Background: Vascular inflammation leading to coronary artery disease (CAD) is a major complication of type 2 diabetes mellitus (T2DM). The chemokine receptor CX3CR1 is a key regulator in vascular injuryrelated inflammation. Objective: The authors examined the T280M and V249I gene variants of the CX3CR1 gene in patients with T2DM, CAD and CAD associated with T2DM, to understand the effect of these polymorphisms on the disease phenotype. Methods: Whole blood samples were collected from 913 South Indian subjects comprising 160 patients with T2DM, 284 with T2DM and CAD, 198 with CAD and 271 healthy subjects. T280M and V249I variants of the CX3CR1 gene were genotyped in these study subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and PCR-DNA sequencing. Results: Multivariate logistic regression analysis revealed that the frequencies of 280M and 249I alleles were higher in controls than in cases in both the CAD and T2DM groups. Adjusted odds of T280M according to logistic regression were significant in all disease groups compared withhealthy subjects. Both MM and II genotypes of T280M and V249I polymorphisms were found to have an atheroprotective role in CAD and T2DM. The association of these polymorphisms were then examined in patients with CAD who were also diagnosed with diabetes. The M allele of T280M polymorphism was associated with attenuated risk for CAD and T2DM. Conclusions: The present study demonstrated a protective role of the T280M variant of CX3CR1 gene for vascular complication in patients with T2DM. This polymorphism may reduce the binding strength of the chemokine receptor, thus attenuating inflammation both in vascular wall and adipose tissue.

Relationship between Urinary Pentosidine Concentration and Vascular Complications in Type 2 Diabetic Patients

Objective: We examined the relationship between urinary pentosidine concentration and vascular complications in patients with type 2 diabetes in order to investigate the pathophysiological roles of pentosidine. Methods: We performed a cross-sectional study in 119 Japanese patients with type 2 diabetes. The correlation of urinary pentosidine concentration with age, diabetes duration, HbA1c and blood glucose levels was investigated. Urinary pentosidine concentration was compared between patients with and without diabetic microvascular complications (retinopathy, nephropathy, and neuropathy), and macrovascular disease. Results: Urinary pentosidine concentration showed a significant positive correlation with age and duration of diabetes. However, it did not correlate with HbA1c, fasting plasma glucose, and postprandial plasma glucose. Patients with diabetic retinopathy showed a significantly higher urinary pentosidine concentration than those without retinopathy. On the other hand, urinary pentosidine concentration did not differ between patients with and without nephropathy, neuropathy, and macrovascular diseases. Stepwise regression analysis demonstrated that age, body mass index, and retinopathy were independent determinants of urinary pentosidine concentration. Logistic regression analysis demonstrated that urinary pentosidine concentration and duration of diabetes were independent determinants of diabetic retinopathy. Conclusion: Urinary pentosidine might have significance as a novel biomarker of retinopathy in patients with type 2 diabetes.

Vascular Complications after Adult to Adult Living Donor Liver Transplantation: Single Center Experience

Objectives: Vascular complications (VC) after living donor liver transplantation (LDLT) are one of the most feared problems that result in graft and patient loss. The aim of this study was to assess the incidence, treatment, and outcome of vascular complications of patients after adult to adult LDLT in a single Egyptian center.

PO361 TESTOSTERON LEVEL AND INSULIN RESISTANCE IN MEN WITH TYPE 2 DIABETES MELLITUS-METABOLIC SYNDROME

Background: Testosterone deficiency often occurs in people with type 2 diabetes mellitus (T2DM) where it contributes to mood and libido disturbances. Total testosterone levels inversely associated with insulin resistance, a factor which has the potential to provide micro and macro vascular complications in patients with T2DM. Several studies in men showed that testosterone supplementation can improve insulin sensitivity conditions. Recent studies have reported that 20–64% of men with testosterone deficiency/hypogonadism also have T2DM. The proportion of men who have both T2DM and hypogonadism increases in older groups of men. Men who have slightly reduced total testosterone level, but not low enough to be considered as testosterone deficiency are also more likely to have low insulin and high blood glucose levels. This study will examine the correlation between total testosterone level and insulin resistance in men with T2DMMetS. Method: This cross sectional study was performed in Surabaya private clinic. Study period was six months between January to June 2014. The variables include: fasting blood sugar, 1 hour post prandial, A1C, HOMA-IR and levels of the total testosterone was measured by radioimmunoassay technique. Low testosterone for patient with T2DM was defined as below 400 ng/dL and normal if above 400 ng/dL. HOMA-IR value more than 2.0 is considered to be positive for IR. Patients on testosterone replacement, and corticosteroids were excluded from this study. Statistical analysis was performed using SPSS 17.0 and Spearmen’s test. Result: Fifty two male subjects were enrolled in this study. The mean age was 62.32±8.72 years old, fasting blood sugar 139.68±43.65mg/dL, blood glucose 1 hour post prandial 255.56±112.06 mg/dL, mean A1C 7.89±1.80%, the mean HOMA-IR 7.14±4.77, while the mean testosterone levels 315.39±251.30 ng/dL. The statistical analysis showed inverse correlation between total testosterone levels and insulin resistance (r: −0.215, p: 0.034) Conclusion: There was a significant inverse correlation between total testosterone level and insulin resistance in this study.

The role of TLR2 and 4-mediated inflammatory pathways in endothelial cells exposed to high glucose.

Postprandial hyperglycemia induces inflammation and endothelial dysfunction resulting in vascular complications in patients with diabetes. Toll-like receptors (TLRs) are central to the regulation of inflammatory responses through activation of nuclear factor-kappa B (NF-ĸB). This study examined the role of TLR2 and 4 in regulating inflammation and endothelial dysfunction when exposed to fluctuating glucose concentrations. HMEC-1 cells (a human microvascular endothelial cell line) were exposed to control (5 mM), 30 mM (high), fluctuating (5/30 mM) and 11.2 mM glucose (approximate glycaemic criteria for the diagnosis of diabetes mellitus) for 72 h. Cells were assessed for TLR2, 4, high mobility group box -1 (HMGB1), NF-ĸB, monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Fluctuating glucose concentrations maximally upregulated TLR4 but not TLR2 expression with increased NF-ĸB activation, IL-8 and ICAM-1 expression. HMGB1 was increased in the supernatants of cells exposed to 30 mM and 11.2 mM glucose compared to control. The addition of recombinant HMGB1 induced NF-ĸB activation and synthesis of proinflammatory cytokines and chemokines, which were prevented by TLR2 or 4 signalling inhibition. An additive effect when both TLR2 and 4 signalling pathways were inhibited was observed. However, only inhibition of TLR4 signalling suppressed the synthesis of MCP-1, IL-8 and ICAM-1. In vivo, streptozotocin-induced diabetic mice exhibited an increase in glomerular ICAM-1 which was not evident in TLR2-/- or TLR4-/- diabetic mice. Collectively, our results suggest that targeting the signalling pathway of TLR2 and 4 may be of therapeutic benefit in attenuating vascular inflammation in diabetic microangiopathy.

The Importance of Assessing Arteriovenous Fistula Patency in the Setting of Persistent Pulmonary Hypertension After Combined Liver Kidney Transplant

Introduction: Portopulmonary hypertension (PoPH) is a well-documented vascular complication in patients with end-stage liver disease. In the setting of left ventricular dysfunction, patients with cirrhosis and ESRD can develop pulmonary venous hypertension. The hemodynamic effects of arteriovenous fistulas (AVFs) in patients with both cirrhosis and ESRD in exacerbating pulmonary arterial and venous hypertension are rarely reported in the literature. A 54-year-old male with a history of 2 renal transplants and a liver transplant for cirrhosis presented with several weeks of progressive dyspnea, orthopnea, and lower extremity edema. His first renal allograft failed due to chronic rejection, requiring him to resume hemodialysis in 2002 through a left upper extremity AVF. He began having recurrent ascites in 2008 and was referred for evaluation of possible liver kidney transplant. His echocardiogram showed an elevated right ventricular systolic pressure of 74.8 mmHg. Subsequent right heart catheterization (RHC) was consistent with pulmonary arterial hypertension, with mean pulmonary arterial pressure (mPAP) 41 mmHg, pulmonary vascular resistance (PVR) 254 dyne*sec/cm5, and cardiac index (CI) 4 dyne*sec/cm5. After 6 months of therapy with sildenafil, his mPAP decreased to 28 mmHg, allowing him to successfully undergo a simultaneous liver kidney transplant in 2009. The patient did well until 3 years later, when he presented with volume overload. Repeat echocardiogram revealed a preserved ejection fraction and a mPAP of 81.6 mmHg. The patent’s RHC revealed a relatively normal PCWP and elevated transpulmonary gradient (TPG) concerning for worsening pulmonary hypertension (mPAP 55 mmHg, PVR 343 dyne*sec/cm5). His symptoms progressed despite receiving aggressive diuresis and ICU support for right ventricular syndrome. Based on the patient’s high cardiac output and pulmonary hypertension with normal PVR, the diagnosis of high output heart failure was made. The patient’s AVF was ligated out of clinical concern for high output through the patient’s fistula causing exacerbation of pulmonary arterial and venous hypertension. Repeat RHC showed decrease in mPAP to 36.6 mmHg 7 months after AVF ligation, consistent with continued improvement of respiratory symptoms with stable liver and kidney allograft function. This case illustrates the potential importance of evaluating graft patency in patients with pre-existing PoPH, given the risk of developing high output heart failure. Given the probability that an AVF will remain patient after renal transplant, clinicians should carefully consider assessing AVF patency and flow in the setting of worsening clinical signs and symptoms suggestive of high-output heart failure.