Cell matrix contact modifies endothelial major histocompatibility complex class II expression in high-glucose environment.

Atherosclerosis is a chronic inflammatory disease. Cardiovascular risk factors such as hyperglycemia, hyperlipidemia, and arterial hypertension induce endothelial dysfunction with alterations in endothelial biosecretion and immune behavior. The aim of this study is to elucidate whether glucose-induced modifications of endothelial biosecretory and immune functions are regulated by interactions of endothelial cells (ECs) with their extracellular matrix [ECs plated on polystyrene-coated tissue culture plates (TC-EC) vs. ECs embedded within three-dimensional (3-D) collagen-based matrixes (3D-EC)]. In the absence of glucose, IFN-γ-induced phosphorylation of JAK and STAT proteins and human leukocyte antigen (HLA)-DR expression were lower in 3D-EC compared with TC-EC. Inversely, the expression of suppressor of cytokine signaling proteins (SOCS)-1 and -3 were significantly higher in naïve 3D-EC compared with naïve TC-EC. IFN-γ-induced upregulation of SOCS proteins was further amplified by the 3-D environment. Glucose significantly augmented IFN-γ-dependent signaling pathways in TC-EC. IFN-γ-induced phosphorylation of JAK and STAT proteins as well as HLA-DR expression by ECs in low- and high-glucose medium was significantly lower in 3-D than in two-dimensional environment. Glucose increased SOCS expression in TC-EC and 3D-EC to the same extent, such that expression levels in 3D-EC exceeded SOCS-1 and -3 expression in TC-EC by 1.6-2.5-fold. In conclusion, low- and high-glucose concentrations amplify IFN-γ-induced signaling pathways in TC-EC. Increased SOCS expression raises the threshold for IFN-γ to induce HLA-DR expression in a 3-D environment. This immunoprotective effect is maintained even in states of experimental hyperglycemia.

Cardiovascular events during World Cup soccer.

BACKGROUND: The Fédération Internationale de Football Association (FIFA) World Cup, held in Germany from June 9 to July 9, 2006, provided an opportunity to examine the relation between emotional stress and the incidence of cardiovascular events. METHODS: Cardiovascular events occurring in patients in the greater Munich area were prospectively assessed by emergency physicians during the World Cup. We compared those events with events that occurred during the control period: May 1 to June 8 and July 10 to July 31, 2006, and May 1 to July 31 in 2003 and 2005. RESULTS: Acute cardiovascular events were assessed in 4279 patients. On days of matches involving the German team, the incidence of cardiac emergencies was 2.66 times that during the control period (95% confidence interval [CI], 2.33 to 3.04; P<0.001); for men, the incidence was 3.26 times that during the control period (95% CI, 2.78 to 3.84; P<0.001), and for women, it was 1.82 times that during the control period (95% CI, 1.44 to 2.31; P<0.001). Among patients with coronary events on days when the German team played, the proportion with known coronary heart disease was 47.0%, as compared with 29.1% of patients with events during the control period. On those days, the highest average incidence of events was observed during the first 2 hours after the beginning of each match. A subanalysis of serious events during that period, as compared with the control period, showed an increase in the incidence of myocardial infarction with ST-segment elevation by a factor of 2.49 (95% CI, 1.47 to 4.23), of myocardial infarction without ST-segment elevation or unstable angina by a factor of 2.61 (95% CI, 2.22 to 3.08), and of cardiac arrhythmia causing major symptoms by a factor of 3.07 (95% CI, 2.32 to 4.06) (P<0.001 for all comparisons). CONCLUSIONS: Viewing a stressful soccer match more than doubles the risk of an acute cardiovascular event. In view of this excess risk, particularly in men with known coronary heart disease, preventive measures are urgently needed.

Transcatheter mitral valve repair may increase eligibility for heart transplant listing in patients with end-stage heart failure and severe secondary mitral regurgitation.

BACKGROUND: Heart transplantation remains the gold standard for treatment of patients with end-stage heart failure and severely reduced ejection fraction (HFrEF). An increased pulmonary vascular resistance (PVR), which is often prevalent in HFrEF patients with secondary mitral regurgitation (SMR), limits the eligibility for transplantation. Therefore, we evaluated whether transcatheter mitral valve repair (TMVr) improves pulmonary circulatory hemodynamics and increases the eligibility for transplantation in end-stage HFrEF patients with severe SMR. METHODS: We retrospectively analysed the hemodynamics by right heart catheterization (RHC) as well as laboratory and clinical outcomes of end-stage HFrEF patients with SMR that underwent TMVr. RESULTS: Seventeen patients (age: 55 ±â€¯10 yrs) underwent TMVr and repeat RHC at a mean follow-up of 5.7 ±â€¯7.9 months. TMVr decreased PVR (3.5 ±â€¯2.2 to 2.3 ±â€¯1.2 wood units, p = 0.02) and systolic pulmonary artery pressure (55.4 ±â€¯15 mmHg to 45.6 ±â€¯9.8 mmHg, p = 0.02) from baseline to follow-up, respectively, while cardiac output was increased (3.7 ±â€¯0.9 l/min to 4.6 ±â€¯1.3 l/min, p = 0.02). In addition, transpulmonary gradient decreased significantly (12.0 ±â€¯7.5 mmHg to 9.7 ±â€¯5.3 mmHg, p = 0.04). The prevalence of New York Heart Association functional class ≥III at follow-up was reduced from 88% (15/17 patients) to 47% (8/17 patients, p = 0.01). All five patients with initially too high PVR (>3.5 WU) showed a significant decrease in PVR and three of them became potential candidates for heart transplantation after TMVr. CONCLUSION: TMVr is associated with reduction in PVR which may increase eligibility for transplantation in some HFrEF patients with severe SMR.

Torsades de Pointes: a rare complication of an extra-adrenal pheochromocytoma.

Pheochromocytoma is an infrequent secondary cause of arterial hypertension, often associated with paroxysmal headache, sweating, weight loss, and palpitations. Cardiovascular complications of pheochromocytoma include sudden death, heart failure due to toxic cardiomyopathy, and hypertensive encephalopathy. Here we report the case of a female with an acquired long-QT-syndrome as a rare complication of an extra-adrenal pheochromocytoma. Diagnosis was made after sotalol-induced Torsades de Pointes.

Effects of corticotropin-releasing hormone (CRH) on endothelin-1 and NO release, mediated by CRH receptor subtype R2: a potential link between stress and endothelial dysfunction?

OBJECTIVE: Psychosocial factors, associated with elevated corticotropin releasing hormone (CRH) concentrations, have been reported to be independently associated with coronary heart disease. METHODS: Endothelin-1 and NO release of human endothelial cells were quantified via ELISA or fluorometrically after treatment with CRH. CRH-receptor subtype 2 (CRH-R2) was visualized on endothelial cells by immunohistochemistry and confirmed by polymerase chain reaction using CRH-R2 primers. RESULTS: CRH induced a significant increase of ET-1 release, and the effect was abolished by the CRH-receptor antagonist astressin. The effect was mediated by CRH-R2. In contrast, NO release was not affected. CONCLUSION: CRH-R2 is expressed on human endothelial cells, mediating the CRH-induced stimulation of ET-1 release, whereas NO release is not affected. Thus, peripherally circulating CRH may offset the balance between endothelial vasoconstrictor and vasodilator release with unopposed vasoconstriction. Our data may provide a new concept on how CRH-receptor antagonists may prevent CRH-induced disorders of vascular biology.

Coronary dilatation after heart transplantation.

BACKGROUND: The angiographic incidence of coronary dilatation (CD) in the nontransplant population is approximately 0.2% to 5%. The endothelial-dependent and -independent causes for CD are postulated. So far, the incidence and prognosis of CD after heart transplantation is unknown. METHODS: We retrospectively analyzed the annual coronary angiographies of 688 heart transplant recipients regarding the incidence of CD (defined as ≥1.5-fold localized increased vessel diameter or diffuse dilatation involving more than 50% of the coronary artery). A subgroup analysis of coronary epicardial (quantitative angiography) and microvascular (doppler flow measurement) vasomotor function in response to acetylcholine (endothelial dependent) and adenosine (endothelial independent) as well as intravascular ultrasound was performed in 177 patients. RESULTS: CD was detectable in 26 patients (3.8%) and was associated with stenosing coronary artery disease in 27% of the patients. Segments with CD tended to have less intimal hyperplasia compared with nondilated segments. A diffuse dilatation (type I-II) was present in 63% of the recipients. The right coronary artery was always involved. The patients with CD (5 of 177) showed a 31% reduced flow velocity in the dilated coronaries compared with the nondilated coronary arteries (P=0.03). Microvascular endothelial-independent function was impaired in CD by -29% (coronary flow reserve mean 1.9 vs. 2.7; P=0.04), whereas endothelial-dependent response was unchanged. Epicardial endothelial-dependent and -independent responses were not different between the groups. Incidence of CD was not associated with limited survival. CONCLUSION: The incidence of CD in the nontransplant population is similar to that in the transplanted population. However, the latter shows a more diffuse extent. Heart transplantation patients with CD had microvascular endothelial-independent functional limitations and flow deceleration, whereas survival was not affected.

Modified serum profiles of inflammatory and vasoconstrictive factors in patients with emotional stress-induced acute coronary syndrome during World Cup Soccer 2006.

OBJECTIVES: We sought to assess whether emotional stress-induced acute coronary syndrome (ACS) is mediated by increased inflammatory and vasoconstrictive mediators. BACKGROUND: The World Cup soccer 2006 has been shown to provoke levels of stress sufficient to increase the incidence of ACS. However, the mechanisms by which stress translates into vascular injury up to plaque rupture still remain elusive. METHODS: Serum levels of soluble CD40L (sCD40L), soluble vascular cell adhesion molecule (sVCAM)-1, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-alpha, high-sensitivity C-reactive protein (hsCRP), regulated on activation, normal T-cell expressed and secreted (RANTES), and endothelin (ET)-1 were determined in patients who experienced an ACS during World Cup matches, in ACS reference patients (not associated with emotional stress), and in healthy volunteers. Correlations and receiver-operating characteristic curves were calculated to develop multivariable analysis and to investigate the diagnostic value of each parameter. RESULTS: The sCD40L, sVCAM-1, MCP-1, TNF-alpha, and ET-1 were significantly higher in study patients compared with the reference group. The hsCRP was similar in both groups, whereas RANTES was decreased in study patients. A positive correlation was found between ET-1 and soccer-induced enhanced levels of sCD40L, sVCAM-1, MCP-1, and TNF-alpha. Receiver-operating characteristic analysis displayed high performance of both MCP-1 and ET-1 as a measure to discriminate between stress-induced ACS and ACS controls. CONCLUSIONS: Stress-induced ACS is associated with a profound increase of inflammatory and vasoconstrictive mediators. The evaluation of a targeted drug delivery, such as anti-inflammatory agents, ET-1 receptor antagonists, or inhibition of endothelin-converting enzyme is warranted to reduce stress-mediated cardiovascular morbidity.

Effects of corticotropin-releasing hormone (CRH) on monocyte function, mediated by CRH-receptor subtype R1 and R2: a potential link between mood disorders and endothelial dysfunction?

Psychosocial factors have been reported to be independently associated with coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the major hormone activated during adaptive responses to stressful stimuli, the undergoing pathophysiological mechanism related to stress-induced endothelial dysfunction is still poorly understood. This study sought to investigate the effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide (NO) release and the receptors involved. Cell adhesion was determined using an adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed by mRNA. Corticotropin-releasing hormone induced a significant time- and concentration-dependent increase of cell adhesion as well as monocytic MAC-1 expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In addition, corticotropin-releasing hormone significantly increased monocytic ET-1 release whereas nitric oxide release was decreased. The effect was abolished by the selective CRH-receptor antagonist astressin. Our findings support the importance of peripherally circulating corticotropin-releasing hormones, by influencing specific homeostatic properties of monocytes. Our data may provide a novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)-related endothelial dysfunction up to cardiovascular complications.