Circulating Adhesion Molecules Research Articles

The effects of exercise training on circulating adhesion molecules in adults: A systematic review and meta-analysis.

The current meta-analysis investigated the effects of exercise training on circulating adhesion molecules i.e. soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in adults. PubMed, Web of Science, Scopus and Embase were searched to identify original articles, published in English languages journal from inception up to 31 August 2023 that compared the effects of exercise training with non-exercising control on sICAM-1 and sVCAM-1 in adults. Standardized mean differences (SMDs) and 95% CIs were calculated using random-effect models. Twenty-three studies including 31 intervention arms and involving 1437 subjects were included in the meta-analysis. Exercise training effectively reduced sICAM-1 [SMD: -0.33 (95% CI -0.56 to -0.11), p = 0.004; I2 = 56.38%, p = 0.001; 23 intervention arms]. Subgroup analyses showed that sICAM-1 decreased in adults with age <60 years (p = 0.01) and BMI ≥ 27 kg/m2 (p = 0.002) and those with metabolic disorders (p = 0.004) and cardiovascular diseases (p = 0.005). In addition, aerobic (p = 0.02) and resistance training (p = 0.007) are effective in reducing sICAM-1. However, exercise training did not indicate a superior effect on sVCAM-1 [SMD: -0.12 (95% CI -0.29 to 0.05), p = 0.17; I2 = 36.29%, p = 0.04; 23 intervention arms]. Our results show that exercise training reduces sICAM-1, but not for sVCAM-1, where both aerobic and resistance training is effective in reducing sICAM-1 in adults with metabolic disorders and cardiovascular diseases. The current meta-analysis was registered at www.crd.york.ac.uk/prospero with ID registration number: CRD42023410474.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

IntroductionMicrocirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. MethodsAdult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. ResultsOf 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). ConclusionsPoor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Does Age Influence Circulating Adhesion Molecules in the Critically Ill?: Retraction.

Does Age Influence Circulating Adhesion Molecules in the Critically Ill?: Retraction.

Retraction Note: The effects of pentoxifylline on circulating adhesion molecules in critically ill patients with acute renal failure treated by continuous veno-venous hemofiltration.

Retraction Note: The effects of pentoxifylline on circulating adhesion molecules in critically ill patients with acute renal failure treated by continuous veno-venous hemofiltration.

Inflammatory and endothelial dysfunction markers in hypertensive patients with type 2 diabetes mellitus

Hypertension and diabetes are two of the main risk factors for the development of cardiovascular disease, and both pathologies overlap significantly in their pathophysiological mechanisms. The aim of this study was to determine the concentration of inflammatory markers and endothelial dysfunction in patients with hypertension and type 2 diabetes mellitus, to compare with healthy individuals, and to determine whether the coexistence of both pathologies has a different effect on the behavior of these markers. A descriptive, correlational, cross-sectional research was carried out from July 2022 to February 2023. A total of 120 individuals were selected for this study (30 controls, 30 with type 2 diabetes mellitus, 30 with hypertension and 30 with diabetes plus hypertension). Each subject had a fasting blood sample drawn for determination of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, ultrasensitive C-reactive protein (hs-CRP), glycosylated hemoglobin, sICAM-1, sE-selectin, IL-6 and TNF-α. A significant increase in the concentration of sICAM-1, sE-selectin, IL-6 and TNF-α was found in diabetic, hypertensive and diabetic patients with hypertension when compared to controls (p&lt;0.0001). The coexistence of diabetes and hypertension did not represent a significant elevation in the concentration of markers of endothelial dysfunction and inflammation. In conclusion, our results suggest endothelial activation as well as an inflammatory state in patients with diabetes and hypertension, indicated by elevated levels of circulating adhesion molecules and proinflammatory cytokines. The simultaneous presence of diabetes and hypertension did not have an additive effect on the levels of these molecules.

Retraction Note: Circulating adhesion molecules in the critically ill: A comparison between trauma and sepsis patients.

Retraction Note: Circulating adhesion molecules in the critically ill: A comparison between trauma and sepsis patients.

A case of early pulmonary embolism following blunt trauma to chest and a long bone fracture: a case report

BackgroundAfter substantial trauma, pulmonary embolism (PE) carries a high risk of morbidity and mortality. Early post-traumatic PE in the absence of deep vein thrombosis (DVT) is a distinct entity that might be connected to rare mechanisms or unidentified biochemical processes.Case presentationA driver of a car was presented with worsening chest pain and shortness of breath (SOB) following a road traffic accident in which he suffered an impact on the chest against the steering wheel and a closed fracture of the right femur. Radiological investigations revealed a pulmonary embolism in the left posterior segment pulmonary artery, without evidence of internal chest injuries or DVT within 12 h from the incident. D-dimer, troponin I, and creatinine kinase were elevated without evidence of myocardial infarction or myocardial injury. Other parameters were within the normal range.ConclusionsPossibilities of early PE in the absence of detectable DVT could be due to hyper-coagulability states, clots from the lower extremity completely getting detached and embolizing to the pulmonary circulation, screening errors, and “de novo” thrombi in the pulmonary circulation. Chest trauma is an identified risk factor for early or late pulmonary embolism. Action of the post-traumatic adrenergic response causing vascular endothelial inflammation and the synthesis of circulating adhesion molecules leading to localized thrombosis have also been suggested as causes for this phenomenon. A greater understanding of rare risk factors for early PE and the possibility of rare complications of chest trauma is useful in detecting and treating them in time, reducing morbidity and mortality.

Impact of maternal diabetes exposure on soluble adhesion molecules in the offspring

Background and aimsSoluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. This study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum and soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) exposed to high glucose concentrations. Methods and resultsWomen with and without diabetes were recruited. DM was diagnosed based on the American Diabetes Association criteria. Primary cultures of HUVEC were cultured in 5 mM and 25 mM glucose with 25 mM mannitol osmotic control. The soluble adhesion molecules, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and conditioned HUVEC media. The mothers with DM were older with higher BMI (p = 0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p = 0.046), but ICAM and E-selectin were not different. ICAM was also significantly correlated with maternal HbA1c (r2 = 0.16, p = 0.004) and cord serum non-esterified fatty acids (r2 = 0.08, p = 0.013). From the HUVEC media, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2 = 0.27, p = 0.010) and cord serum c-peptide (R2 = 0.19, p = 0.043). ConclusionsAlterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease.

HIV-infected patients display increased proatherogenic anti-apolipoprotein A1 autoantibodies, inflammatory and metabolomic markers

Abstract Background HIV-infected patients display an increased risk of cardiovascular events. HIV and antiretroviral therapy (ART) have both been suggested to increase this risk but their specific role remains unclear. Autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) are also associated with cardiovascular risk. The aim of this study was to analyse anti-apoA1 IgG levels and inflammatory markers as well as the metabolomic profile in a cohort of HIV-free, ART-experienced and naïve HIV-infected patients. Methods 144 participants from a South African cohort were categorised into HIV-free (n=50), HIV-infected/ART-experienced (n=50) and HIV-infected/ART-naïve (n=44) groups. The levels of anti-apoA1 IgG were assessed by homemade ELISA assays. We performed targeted metabolomic analyses using standard operating procedures and measured inflammatory biomarkers using the Meso Scale Discovery® platform. Additionally, we conducted in vitro experiments on human aortic endothelial cells treated with anti-apoA1 IgG and assessed levels of adhesion molecules. Results Inflammatory markers (IFNg, IL-6, IL-10, TNFa, CRP all p&amp;lt;0.05), circulating adhesion molecules (ICAM-1 and VCAM-1, p&amp;lt;0.05), anti-apoA1 IgG levels were increased in HIV-infected patients compared to HIV-free participants. While ART treatment significantly reduced IFNg, IL-10, TNFa, VCAM-1, anti-apoA1 IgG levels, no significant differences were observed in other biomarkers between ART-experienced and naïve participants. Treatment of human aortic endothelial cells with anti-apoA1 IgG (40μg/ml) induced a significant increase in these adhesion molecules compared to cells treated with control IgG (40μg/ml). Metabolomic analyses identified 257 endogenous circulating metabolites in plasma. Among these metabolites, we found that in HIV-free and infected patients 14 and 17 metabolites were significantly correlated with anti-apoA1 IgG levels, respectively. Among these 17 metabolites, 2 were positively correlated with the tryptophan pathway; kynurenine (r=0.292, p=0.0069) and 5-hydroxyindolacetate (r=0.316, p=0.0019). Interestingly, kynurenine was not significantly correlated with anti-apoA1 IgG levels in HIV-free patients. Conclusion HIV-infected patients displayed a more proatherogenic profile compared to HIV-free subjects. Anti-apoA1 IgG induced adhesion molecules expression. Metabolomics identified metabolites that were significantly associated with anti-apoA1 IgG levels and inflammatory biomarkers known to underlie atherosclerosis burden. Funding Acknowledgement Type of funding sources: None.

Increased levels of VCAM-1 is associated with higher occurrence of coronary artery disease in adults with moderate to severe obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) leads to important vascular abnormalities, including the endothelial dysfunction and the production of endothelial cell adhesion molecules. The adhesion molecules play an important role in the process of endothelial dysfunction in the pathogenesis of atherosclerosis. We assess the relationship between the levels of adhesion molecules and the presence of coronary artery disease (CAD) in Chinese adults with moderate to severe OSA. MethodsThe cross-sectional study included a total of 189 Chinese adults: 90 patients with moderate to severe OSA (apnea-hypopnea index≥15 events/h) alone, 40 patients with moderate to severe OSA and CAD, and 59 controls without OSA or with mild OSA and without CAD. We used high-throughput Multiplex Immunobead Assay technology to simultaneously test plasma levels of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The associations between the levels of circulating adhesion molecules and CAD in moderate to severe OSA patients were evaluated by multivariate logistic regression analysis. ResultsThe circulating VCAM-1 levels were significantly elevated in patients suffering from moderate to severe OSA combined CAD compared with patients having moderate to severe OSA alone [853.28 (564.26) vs. 416.61 (301.69) ng/mL, P < 0.001]. Furthermore, circulating VCAM-1 levels were independently associated with CAD (odds ration = 2.113, 95%CI 1.400–2.766, P < 0.001) and showed higher discriminatory accuracy in assessing the presence of CAD (AUC: 0.899, 95%CI 0.849–0.950, P < 0.001) in moderate to severe OSA patients. However, no significant association was found between circulating ICAM-1 levels and CAD in moderate to severe OSA patients. ConclusionsThe circulating VCAM-1 levels were significantly correlated with the presence of CAD in Chinese adults with moderate to severe OSA. The circulating VCAM-1 may function as a novel biomarker for monitoring the development and progression of CAD in patients with moderate to severe OSA.

154-LB: Impact of Maternal Diabetes Exposure on Soluble Adhesion Molecules

Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. The current study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum as well as soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) upon exposure to high levels of glucose. Women with and without diabetes (DM; gestational or type 2) were recruited at delivery. DM was diagnosed based on the criteria by the American Diabetes Association. Primary cultures of HUVEC were established in M199 medium with growth supplements. For the high glucose treatment, medium was adjusted to a final glucose concentration of 25mM with media collected 48 hours post treatment. The soluble adhesion molecules intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and the conditioned HUVEC media. Serum adhesion molecules were measured in 42 infants born to mothers with normal glycemia and 35 infants of mothers with DM. The mothers with DM were older with higher BMI (p=0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p=0.046), but ICAM and E-selectin were not different. ICAM was significantly correlated with E-selectin (r2=0.25, p&amp;lt;0.001), but not VCAM. ICAM was also significantly correlated with maternal HbA1c (r2=0.16, p=0.004) and cord serum non-esterified fatty acids (r2=0.08, p=0.013). From the HUVEC, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2=0.27, p=0.010) and cord serum insulin (r2=0.19, p=0.042). Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease. Disclosure S. B. Landreth: None. A. M. Teague: None. M. Jensen: None. S. Gulati: None. J. B. Tryggestad: None. Funding National Institutes of Health (1K23DK106533)

Retraction notice to “Circulating adhesion molecules in cardiac operations: influence of high-dose aprotinin” [Ann Thorac Surg 59 (1995) 100-105

Retraction notice to “Circulating adhesion molecules in cardiac operations: influence of high-dose aprotinin” [Ann Thorac Surg 59 (1995) 100-105

Retraction notice to “Are circulating adhesion molecules specifically changed in cardiac surgical patients?” [Ann Thorac Surg 65 (1998) 608-614

Retraction notice to “Are circulating adhesion molecules specifically changed in cardiac surgical patients?” [Ann Thorac Surg 65 (1998) 608-614

Evaluation of antiretroviral therapy on metabolomics and atherogenic markers in HIV patients

Abstract Background HIV-infected patients display an increased risk of cardiovascular events. HIV and antiretroviral therapy (ART) have both been suggested to increase the risk of cardiovascular events but their specific role remains unclear. Purpose The aim of this study was to analyse the metabolomic profile in a cohort of HIV-free, ART experienced and naïve HIV-infected patients and to identify the metabolite associated with atherosclerosis development and endothelial dysfunction. The impact of ART on inflammatory and autoimmune biomarkers known to underlie atherosclerosis burden was also investigated. Methods 144 participants from a South African cohort were divided in three groups: HIV-free (n=50), HIV-infected/ART experienced (n=50) and HIV-infected/ART naïve (n=44). Targeted metabolomic analyses were performed using standard operating procedures. Atherosclerosis development was evaluated using coronary intima-media thickness (CITM) and endothelial dysfunction by flow-mediated dilation (FMD). Inflammatory biomarkers were measured with the Meso Scale Discovery® platform. The levels of autoantibodies against apolipoprotein A1 (anti-apoA1 IgG) and its specific C-terminal domain (anti-F3L1) levels were assessed by homemade ELISA assays. Results 257 endogenous metabolites were identified in the 144 samples. Regarding the association of metabolites with the vascular markers, eight metabolites were found to be associated with FMD and eleven with CIMT. Among these metabolites, cytosine was negatively correlated with FMD (r=−0.22, p=0.009), while positively with CIMT (r=0.20, p=0.026). Interestingly, from the list of these 18 metabolites, ART-experienced patients displayed an increase in kynurenine (p=0.0007) and 3–2-hydroxyphenyl-propanoate (p=0.0009) levels and a decrease in itaconate (p=0.021) levels compared to ART-naïve patients. HIV-infected patients displayed a more proatherogenic profile compared to HIV-free subjects. Inflammatory markers (IFNg, IL-6, IL-10, TNFα, CRP all p&amp;lt;0.05), circulating adhesion molecules (ICAM-1 and VCAM-1, p&amp;lt;0.05), anti-apoA1 IgG and anti-F3L1 (p&amp;lt;0.05) and CIMT (p=0.05) were increased while FMD (p=0.054) was decreased in HIV-infected patients compared to HIV-free participants. While ART treatment significantly reduced IFNg, IL-10, TNFα, VCAM-1, anti-apoA1 IgG and anti-F3L1, no significant differences were observed in other biomarkers between ART-experienced and naïve participants. Conclusion Metabolomic analysis identified metabolites that were differentially expressed in the 3 groups. 18 metabolites were significantly correlated with FMD or CITM, among which the levels of kynurenine, 3–2-hydroxyphenyl-propanoate and itaconate were modulated by ART. HIV patients displayed increased levels of inflammatory markers, circulating adhesion molecules and anti-apoA1 IgG which was downregulated by ART. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fondation De Reuter; Fondation Schmidheiny; Fondation Prévot; SwissLife AG; Fondation pour la lutte pour le cancer et la recherche bio-médicale

Distinct Effects of Milk-Derived and Fermented Dairy Protein on Gut Microbiota and Cardiometabolic Markers in Diet-Induced Obese Mice

Recent meta-analyses suggest that the consumption of fermented dairy products reduces type 2 diabetes and cardiovascular disease (CVD) risk, although the underlying mechanisms remain unclear. We evaluated whether dairy protein products modulated gut microbiota and cardiometabolic features in mouse models of diet-induced obesity and CVD. Eight-week-old C57BL/6J wild-type (WT) and LDLr-/-ApoB100/100 (LRKO) male mice were fed for 12 and 24 wk, respectively, with a high-fat/high-sucrose diet [66%kcal lipids, 22%kcal carbohydrates (100% sucrose), 12%kcal proteins]. The protein sources of the 4 diets were 100% nondairy protein (NDP), or 50% of the NDP energy replaced by milk (MP), milk fermented by Lactobacillus helveticus (FMP), or Greek-style yogurt (YP) protein. Fecal 16S rRNA gene-based amplicon sequencing, intestinal gene expression, and glucose tolerance test were conducted. Hepatic inflammation and circulating adhesion molecules were measured by multiplex assays. Feeding WT mice for 12 wk led to a 74% increase in body weight, whereas after 24 wk the LRKO mice had a 101.5% increase compared with initial body weight. Compared with NDP and MP, the consumption of FMP and YP modulated the gut microbiota composition in a similar clustering pattern, upregulating the Streptococcus genus in both genotypes. In WT mice, feeding YP compared with NDP increased the expression of genes involved in jejunal (Reg3b, 7.3-fold, P=0.049) and ileal (Ocln, 1.7-fold, P=0.047; Il1-β,1.7-fold, P=0.038; Nos2, 3.8-fold, P=0.018) immunity and integrity. In LRKO mice, feeding YP compared with MP improved insulin sensitivity by 65% (P=0.039). In LRKO mice, feeding with FMP versus NDP attenuated hepatic inflammation (monocyte chemoattractant protein 1, 2.1-fold, P ˂ 0.0001; IL1-β, 5.7-fold, P=0.0003; INF-γ, 1.7-fold, P=0.002) whereas both FMP [vascular adhesion molecule 1 (VCAM1), 1.3-fold, P=0.0003] and YP (VCAM1, 1.04-fold, P=0.013; intracellular adhesion molecule 1, 1.4-fold, P=0.028) decreased circulating adhesion molecules. Both fermented dairy protein products reduce cardiometabolic risk factors in diet-induced obese mice, possibly by modulating the gut microbiota.

Circulating cell adhesion molecules in metabolically healthy obesity

Background/ObjectivesPeople with metabolically healthy obesity (MHO) may still have an increased risk for cardiovascular mortality compared to metabolically healthy lean (MHL) individuals. However, the mechanisms linking obesity to cardiovascular diseases are not entirely understood. We therefore tested the hypothesis that circulating cell adhesion molecules (CAMs) are higher in MHO compared to MHL individuals.Subjects/MethodsSerum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin and P-selectin were measured in age- and sex-matched groups of MHL (n = 32), MHO categorized into BMI-matched insulin sensitive (IS, n = 32) or insulin resistant (IR) obesity (n = 32) and people with metabolically unhealthy obesity (MUO, n = 32).ResultsIndeed, individuals with MHO have significantly higher sICAM-1, E-selectin, and P-selectin serum concentrations compared to MHL people. However, these CAMs are still significantly lower in IS compared to IR MHO. There was no difference between the groups in sVCAM-1 serum concentrations. Compared to all other groups, circulating adhesion molecules were significantly higher in individuals with MUO.ConclusionsThese findings suggest that obesity-related increased cardiovascular risk is reflected and may be mediated by significantly higher CAMs. The mechanisms causing elevated adhesion molecules even in the absence of overt cardio-metabolic risk factors and whether circulating CAMs could predict cardiovascular events need to be explored.

Reduced levels of circulating adhesion molecules in adolescents with early-onset psychosis

It is suggested that neurodevelopmental abnormalities are involved in the disease mechanisms of psychotic disorders. Although cellular adhesion molecules (CAMs) participate in neurodevelopment, modulate blood–brain barrier permeability, and facilitate leukocyte migration, findings concerning their systemic levels in adults with psychosis are inconsistent. We examined plasma levels and mRNA expression in peripheral blood mononuclear cells (PBMCs) of selected CAMs in adolescents with early-onset psychosis (EOP) aged 12–18 years (n = 37) and age-matched healthy controls (HC) (n = 68). EOP patients exhibited significantly lower circulating levels of soluble platelet selectin (~−22%) and soluble vascular cell adhesion molecule-1 (~−14%) than HC. We found no significant associations with symptom severity. PSEL mRNA expression was increased in PBMCs of patients and significantly negatively correlated to duration of illness. These findings suggest a role for CAMs in the pathophysiology of psychotic disorders.

Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the Treatment Options for type 2 Diabetes in Adolescent and Youth study.

The Treatment Options for type 2 Diabetes in Adolescent and Youth study, a randomized clinical trial of three treatments for type 2 diabetes (T2DM) in youth, demonstrated treatment failure (defined as sustained HbA1c ≥8%, or inability to wean insulin after 3 months after acute metabolic decomposition) in over half of the participants. Given that binding of mononuclear cells to vascular endothelium, initiated by cellular adhesion molecules and chemokines, is an early step in vascular injury, we sought to evaluate (a) changes in cellular adhesion molecule levels during the trial; (b) effect of diabetes treatment; and (c) association of markers with HbA1c, hypertension, hypercholesterolemia, nephropathy, and retinopathy. Participants (n = 515 of 699) that had baseline assessment of adhesion molecules (monocyte chemoattractant protein-1 [MCP-1], vascular cell adhesion marker [VCAM], intercellular adhesion marker [ICAM], and E-Selectin) and at least one other assessment, measured at month 12, 24, or 36, were included. Over 1 to 3 years, significant increases in MCP-1 and decreases in VCAM (both P < .0001) concentrations were found; however, no significant interactions were identified with treatment group for any molecule. For every 1% increase in HbA1c, ICAM increased by 1.8%, VCAM by 1.5%, and E-selectin by 6.8% (all P < .0001). E-selectin increased by 3.7% and 4.2% for every 10 mm Hg increase in systolic and diastolic blood pressure, respectively (both P < .0001). ICAM was 10.2% higher and E-selectin was 15.5% higher in participants with microalbuminuria (both P < .01). There was no significant association of adhesion molecule levels with retinopathy. Concentrations of cellular adhesion molecules rise with increasing HbA1c in youth with T2DM, and are associated with blood pressure and microalbuminuria, markers of vascular injury.

Laboratory Parameters of Hemostasis, Adhesion Molecules, and Inflammation in Type 2 Diabetes Mellitus: Correlation with Glycemic Control.

Background: Type 2 diabetes mellitus (T2DM) is characterized by a prothrombotic state, predisposing to vascular complications. Some related markers, linking thrombophilia to hemostasis and inflammation, however, have been poorly explored in relation to patients’ glycemia. We therefore investigated the association of laboratory hemostatic parameters, circulating adhesion molecules (ADMs), white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) with T2DM and glycemic control. Research design: In this study, 82 subjects, grouped into T2DM patients (n = 41) and healthy individuals (n = 41) were enrolled. To evaluate glycemic control, the T2DM cohort was expanded to 133 patients and sub-classified according to glycated hemoglobin (HbA1c) <7% and ≥ 7% (n = 58 and n = 75, respectively). We assessed glycemia, HbA1c, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), platelet and leukocyte parameters, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectins (E-, P-, L-). Results: PT % activity, PAI-1, VCAM-1, WBC, and neutrophil counts were significantly higher in T2DM patients than in healthy subjects. Poor glycemic control (HbA1c ≥ 7%) was correlated with increased PT activity (p = 0.015), and higher levels of E-selectin (p = 0.009), P-selectin (p = 0.012), and NLR (p = 0.019). Conclusions: Both T2DM and poor glycemic control affect some parameters of hemostasis, inflammation, and adhesion molecules. Further studies are needed to establish their clinical utility as adjuvant markers for cardio-vascular risk in T2DM patients.

The Pro-Adhesive and Reduced Angiogenic Properties of Endothelial Colony Forming Cells (ECFC) from JAK2V617F MPN Patients Are Not Related to the Expression of the JAK2 mutation in These Cells: A Potential Role of ADAM17

INTRODUCTION: JAK2V617F mutation is independently associated with a higher risk of venous thromboembolic events (VTE) in myeloproliferative neoplasms (MPN). We have previously shown that endothelial colony-forming cells (ECFCs) from JAK2V617F MPN patients do not express this mutation but exhibit a pro-adhesive phenotype with a lower in vitro angiogenic potential. Here, we explore the mechanisms through which ECFCs from JAK2V617F MPN patients behave differently from ECFCs from healthy individuals. METHODS: We selected 38 patients with newly or previously diagnosed MPN, regardless of current or prior hydroxyurea therapy, with or without a history of VTE. Plasma levels of ADAMTS13, P-selectin, soluble VCAM, soluble ICAM, PDGF-AA, PDGF-AB/BB, IL-8, IL-1β, and soluble CD40 ligand were measured through the use of a multiplex assay. We then tried to isolate ECFCs from 20 of the JAK2V617F patients as well as 14 healthy individuals. Successfully isolated ECFCs were then submitted to co-culture with red blood cells (RBC), after which RNA was extracted from ECFCs. ADAMTS13, P-selectin, sVCAM, and sICAM were measured in the supernatant from ECFCs and RBC co-culture with multiplex assay. ECFCs' surface expression of P-selectin, VCAM, ICAM, and E-selectin was measured with the use of flow cytometry. Gene expression in RNA from co-cultured ECFCs was assessed with two 84-gene RT-PCR arrays for endothelial cell biology and signal transduction pathways (RT2 Profiler PCR array, Qiagen®). RESULTS: Recruited patients had polycythemia vera (PV) (n=17), primary myelofibrosis (PMF) (n=7) and essential thrombocythemia (ET) (n=14); 34% of them had had a previous VTE (6/17 PV; 3/14 ET and 4/7 PMF). Median age was 59 years (26-88), 23% were male. Compared with JAK2wt, JAK2V617F MPN patients (n=29) showed higher median concentrations of sVCAM (1063 vs. 786.5 ng/ml, p=0.0315), sCD40L (339 vs. 166.4 ng/ml, p=0.0065), PDGF-AA (430.6 vs. 136.5 ng/ml, p=0.03) and PDGF-AB/BB (1068 vs. 365.8 ng/ml, p=0.004). Success in ECFC isolation was 9/20 (45%) in JAK2V617F MPN patients and 8/14 (57%) in healthy individuals. None of the ECFCs from JAK2V617F MPN patients expressed this mutation. In comparison with ECFCs from healthy individuals, ECFCs from JAK2V617F MPN patients did not show a higher expression of either VCAM1, ICAM, P-selectin, and E-selectin, as measured by flow cytometry after co-culture with RBCs. Multiplex assay on the supernatant of this co-culture did not show any difference in the levels of ADAMTS13, sVCAM, sICAM, and sP-selectin. RNA PCR array from the ECFCs after co-culture with RBCs showed no difference in the expression of adhesion molecules when compared with ECFCs from healthy individuals, except for the increased expression of ADAM17 (fold regulation: 5.46, p=0.006), a metalloprotease involved in the shedding of adhesion molecules, among them VCAM1. ECFCs from MPN patients did not show higher activation of the JAK-STAT pathway but had a lower expression of WNT5 (fold regulation: -2.22, p=0.03), indicating a reduced activation of the Hedgehog pathway, suitable with the reduced in vitro angiogenesis capacity of these cells. CONCLUSIONS: JAK2V617F MPNs are associated with an increase in circulating adhesion molecules, such as sVCAM, and platelet activation markers. The pro-adhesive phenotype and lower angiogenic potential of ECFCs JAK2V617F MPN patients are not related to this mutation, which is not expressed in these cells and might be related to an increased expression of ADAM17 and reduced activation of the Hedgehog pathway. Disclosures Ozelo: BioMarin: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Novo Nordisk: Research Funding; Roche: Research Funding.