Markers Of Endothelial Damage Research Articles

Endothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells.

Background:Mature circulating endothelial cells (CEC) are surrogate markers of endothelial damage. CEC measured in patients with advanced cancer are thought not only to derive from damaged normal vasculature (n-CEC), but also from damaged (t-CEC). Therefore, assays that allow the discrimination between these two putative types of CEC are thought to improve the specificity of the enumeration of CEC in cancer.Methods:Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay.Results:No difference in antigen expression between normal and malignant endothelial cells (ECs) was found for CD54, CD109, CD137, CD141, CD144 and CXCR7. In contrast, overexpression for CD105, CD146, CD276 and CD309 was observed in tumour ECs compared with normal ECs. CD276 was most differentially expressed and chosen as a marker for further investigation. CD276-expressing CEC were significantly higher in 15 patients with advanced colorectal cancer (median 9 (range 1–293 cell per 4 ml); P<0.005), in 83 patients with a glioblastoma multiforme (median 10 (range 0–804); P<0.0001) and in 14 patients with advanced breast cancer (median 14 (range 0–390) P<0.05) as compared with 24 healthy individuals (median 3 (range 0–11)). Of all patients with malignancies, 58% had CD276+ CEC counts above the ULN (8 cell per 4 ml).Conclusions:The present study shows that CD276 can be used to discriminate ECs from malignant tissue from ECs from normal tissue. In addition, CD276+ CEC do occur in higher frequencies in patients with advanced cancer.

SAT0030 Circulating Endothelial Microparticles and Endothelial Progenitors Cells in Primary SjÖGren's Syndrome: New Markers of Chronic Endothelial Damage?

BackgroundSubclinical atherosclerosis can be considered a form of systemic involvement in patients with chronic inflammatory joint and connective tissue diseases. Multiple factors, including inflammatory and immune-mediated mechanisms, have been identified...

Prospective assessment of circulating endothelial cells (CECs) as markers of activity of first-line treatment in advanced clear cell renal cell carcinoma (CCRCC): The CIRCLES study (SOGUG 2011-01).

e22019 Background: CECs counts have been proposed as a marker of endothelial damage in CCRCC. However, standardization of the technics of assessment and an homogeneous definition of CECs are lackin...

Association of n-3 polyunsaturated fatty acids with soluble thrombomodulin as a marker of endothelial damage: A cross-sectional pilot study

BackgroundSoluble thrombomodulin (sTM) is a useful marker of vascular endothelial damage. Although n-3 polyunsaturated fatty acids (n-3 PUFAs) (eicosapentaenoic acid: EPA; docosahexaenoic acid: DHA) have various cardiovascular protective effects, their effect in preventing vascular endothelial damage remains unclear. Furthermore, little is known about the association of EPA and DHA with sTM using the cross-sectional study method. Methods and resultsThis pilot study was designed as a hospital-based cross-sectional study to investigate the relationships between serum n-3 PUFA levels and sTM level in patients with the presence of one or more risk factors for atherosclerosis. Of the 534 sequential patients who had routinely been registered to a study cohort of our institute, 324 patients without chronic kidney disease (because sTM is eliminated by renal excretion and the serum sTM level is increased by renal dysfunction) were enrolled in this study. In a multivariate analysis after adjustment for atherosclerotic risk factors, elevated EPA+DHA level was an independent variable of decreased sTM level (β=−0.183, p=0.0006). The serum levels of EPA and DHA showed a strong correlation (r=0.736, p<0.0001); however, multivariate analysis including EPA and DHA revealed that serum DHA (β=−0.243, p=0.003), but not serum EPA (β=0.049, p=0.538), was identified as an independent negative determinant of sTM level. ConclusionAlthough there are numerous unresolved issues in regard to the differences in the cardiovascular protective effects between EPA and DHA, DHA may be associated with a decrease in sTM. A large-scale trial would be warranted to demonstrate whether the beneficial effect of n3-PUFAs therapy on endothelial damage and improvement of endothelial function might also result in fewer clinical cardiovascular events.

Polymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population

The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, G>A) and rs836478 (intron 3, T>C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort. Two hundred two normotensive (NT) subjects (aged 4-16 years) were divided into 2 groups: NT subjects with hypertensive parents (NH; n = 103) and NT subjects with NT parents (NN; n = 99). We measured markers of inflammation (high-sensitivity C-reactive protein, interleukin 6 (IL-6), interleukin 8, and tumor necrosis factor α), endothelial damage (Plasminogen activator inhibitor-1 metalloproteinase-9, and metalloproteinase-2), and oxidative stress (malondialdehyde). Data were expressed as median and interquartile range (IQR). We found differences in polymorphism rs836478 (intron 3, C>T) in both genotypic (χ(2) = 15.2, 2 df; P = 0.0005) and allelic (X(2)=5.5, 1 df; P = 0.01) frequencies in NH vs. NN subjects. NH subjects with a TT genotype showed increase MMP9 expression (median = 2.3, IQR - 1.6-3.2; vs. median = 1.6, IQR = 1.6-2.3 AU; P = 0.01) and lower IL-6 expression (median = 8.8, IQR = 7.0-11.8; vs. median = 12.1, IQR = 8.2-14.7 pg/ml; P = 0.02) compared with subjects with TC/CC genotype. No difference in the allelic frequency distribution was seen in the polymorphism rs10951982 (NH vs. NN: χ(2)=0.2, 1 df; P = 0.6). For this SNP, NN subjects with GA/AA genotype showed decreased diastolic BP indexes compared with subjects with native GG genotype (median = 1.08, IQR = 1.0-1.2; vs. median = 0.99, IQR = 0.94-1.1; P = 0.02). We report the frequency of polymorphisms rs836478 and rs10951982 of the RAC1 gene in a Spanish-Amerindian cohort. The polymorphism rs836478 was associated with an increased expression in markers of inflammation and endothelial damage (MMP9 and IL-6) in pediatric subjects with a hypertensive genetic background.

Markers of endothelial damage and repair in Takayasu arteritis: Are they associated with disease activity?

The current clinical and laboratory parameters of Takayasu arteritis (TA) are insufficient for proper assessment of disease activity. The aims of this study were to investigate the markers of endothelial injury and repair, including circulating endothelial cell (CEC), circulating endothelial progenitor cell (CEPC) and vascular endothelial growth factor (VEGF), and evaluate their associations with disease activity in patients with TA. Thirty-two patients with TA and 30 healthy age- and sex-matched controls were included in this study. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, the Indian Takayasu's Arteritis Scoring (ITAS2010) and physician's global assessment (PGA). CECs and CEPCs were measured by flow cytometry, and VEGF was measured using an enzyme-linked immunosorbent assay. The CEC level was found to be higher in TA patients than in the healthy controls (HC) (p < 0.001). There was no significant difference in CEC level between the active and inactive patients, but its level was slightly correlated with C-reactive protein (CRP) level. CEPC and VEGF levels in TA patients with active disease were higher than those in the inactive patients and HC. CEPC and VEGF levels were positively correlated with ITAS-CRP and PGA scores. This study shows increased level of CEC in patients with TA. It also suggests that the CEPC and VEGF levels may be correlated with disease activity.

Closer look at white-coat hypertension.

This review aims to clarify novel concepts regarding the clinical and laboratory aspects of white-coat hypertension (WCHT). Recent studies on the clinical and biological implications of WCHT were compared with existing knowledge. Studies were included if the WCHT patients were defined according to the 2013 European Society of Hypertension guidelines, i.e., an office blood pressure (BP) of ≥ 140/90 mmHg, a home BP of ≤ 135/85 mmHg, and a mean 24-h ambulatory BP of ≤ 130/80 mmHg. WCHT studies published since 2000 were selected, although a few studies performed before 2000 were used for comparative purposes. True WCHT was defined as normal ABPM and home BP readings, and partial WCHT was defined as an abnormality in one of these two readings. The reported prevalence of WCHT was 15%-45%. The incidence of WCHT tended to be higher in females and in non-smokers. Compared with normotensive (NT) patients, WCHT was associated with a higher left ventricular mass index, higher lipid levels, impaired fasting glucose, and decreased arterial compliance. The circadian rhythm in WCHT patients was more variable than in NT patient's, with a higher pulse pressure and non-dipping characteristics. Compared with sustained hypertension patients, WCHT patients have a better 10-year prognosis; compared with NT patients, WCHT patients have a similar stroke risk, but receive more frequent drug treatment. There are conflicting results regarding WCHT and markers of endothelial damage, oxidative stress and inflammation, and the data imply that WCHT patients may have a worse prognosis. Nitric oxide levels are lower, and oxidative stress parameters are higher in WCHT patients than in NT patients, whereas the antioxidant capacity is lower in WCHT patients than in NT patients. Clinicians should be aware of the risk factors associated with WCHT and patients should be closely monitored especially to identify target organ damage and metabolic syndrome.

Effect of a fixed dose of fresh frozen plasma on systemic inflammation and endothelial damage in nonbleeding critically ill patients

Fresh frozen plasma (FFP) is associated with onset of acute lung injury [1], the mechanism of which is largely unknown. On the other hand, FFP may be beneficial, as a higher ratio of FFP to red blood cells decreases mortality in bleeding trauma patients [2] and is associated with an endothelial stabilizing effect in vitro [3]. We investigated the effect of transfusion with FFP on host response and markers of endothelial damage in nonbleeding critically ill patients.

Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk

The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.

Blood Markers of Coagulation, Fibrinolysis, Endothelial Dysfunction and Inflammation in Lacunar Stroke versus Non-Lacunar Stroke and Non-Stroke: Systematic Review and Meta-Analysis

Background: The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general. Summary: We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in lacunar stroke versus non-stroke. Compared to other ischaemic stroke subtypes, homocysteine did not differ in lacunar stroke while vWF was significantly lower in lacunar stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in lacunar stroke versus non-stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between lacunar stroke and non-stroke. Compared to other ischaemic stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to lacunar stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in lacunar stroke acutely, with insufficient data chronically. Key Messages: Lacunar stroke is an important stroke subtype. More studies comparing lacunar stroke to non-lacunar stroke specifically, rather than to non-stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with lacunar stroke and cerebral small vessel disease.

The intriguing issue of genetic predisposition and the importance of identification of pre-clinical markers of endothelial damage in radiotherapy-induced cardiotoxicity: reply

We thank Dr Gallucci for her letter about the joint EACVI/ASE expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults.1 As underlined, there is compelling evidence that chest radiotherapy can increase the risk of heart disease. Although modern radiotherapy techniques are likely to reduce the prevalence and severity of radiation-induced heart disease (RIHD), the incidence of RIHD is expected to increase in cancer survivors who have received old radiotherapy regimens. The pathophysiology of RIHD remains poorly understood. Genetic and exogenous factors certainly enhance the risk of RIHD and contribute to inter-patient disease expression differences.2 As exogenous factors have been shown to result in genomic instability, and as low-dose radiation induces long-lasting genomic instability, synergistic interaction between radiation-induced effects and pathogenic events unrelated to radiation exposure is highly probable. When normal tissues are irradiated, identifying factors modulating their sensitivity to radiation is paramount but challenging. Little is known about the genetic variants of RIHD. Recently, …

The intriguing issue of genetic predisposition and the importance of identification of pre-clinical markers of endothelial damage in radiotherapy-induced cardiotoxicity

We have read with great interest the article ‘Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography’ by Lancellotti et al .1 Late cardiovascular complications after chest radiotherapy (RT), even modern RT techniques, are a remarkably increasing problem. Care of cancer survivors is becoming an emergent and topic issue especially after chest irradiation and more so for left breast cancer patients.2 In this subset of patients, RT should be addressed a risk factor for coronary artery disease (CAD) and …

Circulating Endothelial Cells Enumeration Is a Helpful Tool In The Diagnosis Of GvHD In Patients Undergoing Allogeneic Hematopoietic Stem Cells Transplantation

Allo-HSCT can be burdened by life-threatening complications, being GvHD the major cause of morbility and mortality. Clinical and physio-pathological evidences showed that vascular endothelium could be a target of GvHD in very early phase; therefore markers of endothelial damage are warranted as valuable support in GvHD diagnosis. We conducted a study with primary endpoint to identify and count circulating endothelial cells (CEC) in peripheral blood of patients undergoing allo-HSCT as a function of endothelial damage.The CellSearch System® is used to capture and enumerate CEC. Enriched and stained cells are dispensed into a MagNest® cartridge that is scanned and individual images of cells are scored as CEC, based on CD146+, CD105+, DAPI+ and CD45- phenotype. Patients undergoing allo-HSCT were tested before (T1), after the conditioning regimen (T2), at engraftment (T3), at GvHD onset (T4) and at 1 weeks after steroids treatment (T5). Ten healthy subjects served as controls.We enrolled 40 patients with hematologic neoplastic diseases (7 HD, 13 AML, 5 ALL, 8 MM, 3 CLL, 1 NHL, 1 CML, 2 SAA) undergoing allo-HSCT from either HLA-matched familial (n=12) or unrelated donor (n=28). GvHD (grade I-IV) manifested in 19/39 patients. No clinical and transplant characteristics differences were present between patients with and without GvHD. The median CEC/ml pre allo-HSCT was 20 (n=40, range 4-718), in comparison to a value of 2 (range 1-14) in the 10 healthy subjects. At time of engraftment CEC/ml were 47 (range 16-148) in patients with GvHD and 92 (range 23-276) in patients without GvHD (P=0.006). This difference remained significant in multivariate analysis by logistic regression model (OR 0.97, 95% C.I. 0.96-0.99; P=0.02). At GvHD onset, the relative increase of CEC counts (T4 vs T3) was 44% (range, -43 - 569%) in GvHD patients versus 0% (range, -49 – 2%) in patients without GvHD (P=0.003), being confirmed in multivariate analysis (OR 1.04, 95% C.I. 1.0-1.08; P=0.04).Circulating endothelial cells can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT. The confirmation of the clinical utility of CEC counts in a larger series of patients, together with the use of a semi-automatic, standardized and reproducible technology, will allow a valuable help in the diagnostic definition of GvHD in early phase, and moreover could be a valid complement in the prognostic stratification of patients candidates to allo-HSCT. Disclosures:No relevant conflicts of interest to declare.

The role of soluble thrombomodulin in the risk stratification and prognosis evaluation of septic patients in the emergency department

Soluble thrombomodulin (sTM) is a sensitive marker of endothelial damage. In this study we investigated the role of sTM in the evaluation of the severity and prognosis of septic patients in the emergency department (ED). A prospective, observational cohort study was performed in the ED of an urban, university hospital. Patients who had suspected infection with two or more criteria of systemic inflammatory response syndrome were consecutively enrolled. sTM, D-Dimer and procalcitonin levels were measured on enrollment, and the Mortality in Emergency Department Sepsis (MEDS) score was calculated. A 30-day follow-up was performed for all patients. A total of 372 patients with sepsis, 210 patients with severe sepsis and 98 patients with septic shock were enrolled in this study. According to the disease severity, patients were divided into sepsis subgroup and severe sepsis subgroup (including septic shock). In addition, patients were divided into survivors subgroup and non-survivors subgroup according to the 30-day mortality. Plasma sTM levels in patients with severe sepsis were higher than those with sepsis (P<0.001). Compared with survivors, non-survivors has higher plasma sTM levels (P<0.001). Multivariate logistic regression analysis showed that sTM was an independent predictor of severe sepsis (odds ratio 1.11) and 30-day mortality (odds ratio 1.059). Receiver operating characteristic curve analysis showed that sTM was a useful parameter in prediction of severe sepsis (0.859) and 30-day mortality (0.78). Compared with the MEDS score alone, combination of sTM and the MEDS score can improve the accuracy in prediction of severe sepsis and 30-day mortality. sTM is a valuable biomarker in the risk stratification and prognosis evaluation of ED sepsis. Furthermore, sTM can enhance the ability of the MEDS score in prediction of severe sepsis and 30-day mortality.

OP0038 Effects of Angiotensin II Receptor Blockade in Systemic Sclerosis: Randomized Controlled Trial

BackgroundSystemic sclerosis (SSc) is characterized by fibrosis and widespread vascular pathology. Initial events involve endothelial cell damage, loss of normal vasodilatory mediators and excessive vasoconstriction. Previous studies have demonstrated that...

AB1056 Aortic calcification on lumbar spine radiographs: Is it important?

BackgroundVascular calcification is a marker of endothelial cell damage and is associated with cardiovascular morbidity. Calcification of the abdominal aorta (AA) is occasionally noted as an incidental finding on lumbar...

THU0174 Endothelial microparticles and circulating endothelial progenitor cells in primary sjægren’s syndrome patients: A potential marker of endothelial damage?

BackgroundPatients with systemic inflammatory and autoimmune diseases display an increased risk of cardiovascular (CV) mortality. Inflammatory and immune-mediated mechanisms have been identified to promote induction and progression of atherosclerotic endothelial...

Selective Intrauterine Growth Restriction in Monochorionic Twin Pregnancies: Markers of Endothelial Damage and Metabolomic Profile

The aim of this study was to assess the aorta-intima thickness (aIT) and serum metabolomic profile in selective intrauterine growth-restricted (sIUGR) monochorionic diamniotic (MCDA) twin fetuses presenting Doppler velocimetry alterations. Fetal abdominal aIT was measured by ultrasound at 32 weeks of gestation, enrolling 24 MCDA twin fetuses (8 sIUGR and 16 controls). sIUGR twin fetuses were classified into two groups: Group 1 consisted of sIUGR with abnormal umbilical artery (UA) Doppler waveforms and Group 2 included sIUGR with normal UA Doppler. Group 3 were control fetuses appropriate for gestational age (AGA). Fetal blood samples were obtained from the umbilical vein immediately after fetal extraction. A non-targeted metabolomic profiling investigated fetal metabolism alterations by using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Median fetal aIT was significantly larger in Group 1 (median value = 0.9 mm; range = 0.8-1.0 mm; p < .002) and Group 2 (median value = 0.8 mm; range = 0.7-0.8 mm; p < .002) than in AGA Group 3 (median value = 0.5 mm; range = 0.4-0.6 mm; p < .002). Metabolomic analyses, performed on four sIUGR cases (Group 1) compared with four AGA co-twins, showed an upregulation of phenylalanine, sphingosine, glycerophosphocholine, and choline, and a downregulation of valine, tryptophan, isoleucine, and proline sIUGR Group 1 compared with AGA. Although for metabolomics data only a statistical tendency (and not a statistical significance) was reached due to the small sample size, we believe that our results represent a valid starting point for further in-depth metabolomic and proteomic investigations of sIUGR in MCDA fetuses.

Stress-Induced Hyperviscosity in the Pathophysiology of Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TC) is characterized by transient hypokinesis of the left ventricular apex or midventricular segments with coronary arteries without significant stenosis. It is often associated with emotional or physical stress; however, its pathophysiology is still unclear. In the present study, we analyzed the alterations in blood viscosity and markers of endothelial damage induced by sympathetic stimulation in patients with previous TC. Seventeen women (mean age 71 years) with previous TC, included and investigated in the TC Tuscany Registry, were compared to a control group of 8 age- and risk factor-matched women with chest pain and coronary arteries free of stenosis. All subjects underwent the cold pressor test (CPT). Before and after the CPT, the hemorheologic parameters (whole blood viscosity at 0.512 s(-1) and 94.5 s(-1), plasma viscosity, erythrocyte deformability index, and erythrocyte aggregation), catecholamines, plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor levels were assessed. The patients with TC had significantly greater baseline PAI-1 levels (p <0.01) and lower erythrocyte deformability index values (p <0.01). After CPT, both the patients with TC and the controls had a significant increase in several hemorheologic parameters, catecholamines, and von Willebrand factor levels and a decrease in erythrocyte deformability index. However, the PAI-1 levels were significantly increased only in the patients with TC. Compared to the controls, the patients with TC had significantly greater values of whole blood viscosity at 94.5 s(-1) (p <0.05), PAI-1 (p <0.01), von Willebrand factor (p <0.05) and lower erythrocyte deformability index values (p <0.01) after CPT. In conclusion, the results of the present study suggest that in patients with TC, the alterations in erythrocyte membranes and endothelial integrity induced by catecholaminergic storm could determine microvascular hypoperfusion, possibly favoring the occurrence of left ventricular ballooning.

Differences in the released endothelial microparticle subtypes between human pulmonary microvascular endothelial cells and aortic endothelial cells in vitro

ABSTRACTCirculating endothelial microparticles (EMPs) are membrane vesicles that are shed into the blood stream from activated or apoptotic endothelial cells. We previously reported that circulating EMP numbers significantly increased in stable chronic obstructive pulmonary disease (COPD) patients and during exacerbation compared with healthy control subjects. However, different types of circulating EMPs with distinct time profiles were detectable during exacerbations. We hypothesized that the released EMP subtypes correlated with differences in the inflammatory stimuli and the endothelial cell type. We compared the EMP subtypes from human aortic endothelial cells (Aortic ECs) and human lung microvascular endothelial cells (Pulmonary microvascular ECs) released in response to various stimuli, including proinflammatory cytokines (TNFα), oxidative stress (H2O2), and cigarette smoke extracts (CSE) in vitro. We defined circulating EMPs by the expression of endothelial antigens: CD144+ MPs (VE-cadherin EMPs), CD31+/CD41− MPs (PECAM EMPs), CD62E+ MPs (E-selectin EMPs), and CD146+ MPs (MCAM EMPs). E-selectin EMPs were released from both pulmonary microvascular and aortic ECs in response to TNFα but not to H2O2 or CSE stimulation. The amount of MCAM EMPs released from pulmonary microvascular ECs differed significantly between the cells stimulated with H2O2 and those stimulated with CSE. VE-cadherin EMPs were only released from aortic ECs, whereas PECAM EMPs were released exclusively from pulmonary microvascular ECs. The EMP subtypes released differ in vitro among TNFα, H2O2, and CSE stimulation as well as between pulmonary microvascular and aortic ECs. The differences in circulating EMP subtypes may reflect a condition or site of endothelial injury and may serve as markers for endothelial damage in COPD patients.