CD40 ligand inhibits endothelial cell migration by increasing production of endothelial reactive oxygen species

Background— The CD40/CD40 ligand system is involved in atherogenesis. Activated T lymphocytes and platelets, which express high amounts of CD40 ligand (CD40L) on their surface, contribute significantly to plaque instability with ensuing thrombus formation, leading to acute coronary syndromes. Because reendothelialization may play a pivotal role for plaque stabilization, we investigated a potential role of CD40L on endothelial cell (EC) migration

Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells

Background— Transplantation of ex vivo expanded circulating endothelial progenitor cells (EPCs) from peripheral blood mononuclear cells improves the neovascularization after critical ischemia. However, the origin of the endothelial progenitor lineage and its characteristics have not yet been clearly defined. Therefore, we investigated whether the phenotype and functional capacity of EPCs to improve neovascularization depend on their monocytic origin

Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling

Background— Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular function after experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs

The effects of atorvastatin therapy on endothelıal function in patients with coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Statins improve the endothelial function in patients with coronary artery disease (CAD). However, they contribute to the substantial decrease in coronary heart disease by reducing plasma cholesterol levels. They also, reduce oxidative stress, stabilize the atherosclerotic plaque and inhibit inflammatory response. These functions of statins have been briefly described as pleiotropic effects. The aim of our study was to evaluate the effect of atorvastatin therapy on endothelial functions in patients with CAD.</p> <p>Methods</p> <p>Fourty-nine patients (40 men, 9 women, mean age 59 +/- 11 years) with diagnosed CAD were selected as the study group. The patients were given 10 mg/day atorvastatin for 12 weeks. If the target cholesterol levels has not been achieved 6 weeks after the treatment, then the daily atorvastatin dosage has been increased. The endothelial function was evaluated by flow mediated dilatation (FMD) of the brachial artery.</p> <p>Results</p> <p>It has been figured out that 12 weeks later, atorvastatin caused a statistically significant decrease in the plasma levels of LDL-cholesterol and total cholesterol (p < 0,0001). Meanwhile, it was determined that the FMD got statistically significant improved 12 weeks after the atorvastatin therapy (8,1%–4,2%, p < 0,001). However there was no statistically significant change in non-endothelium dependent dilatation (NID).</p> <p>Conclusion</p> <p>Endothelium derived vasodilatation (EBD), which was non-invasively detected via brachial artery ultrasonography, had statistically significant improvment within 12 weeks of atorvastatin therapy whereas non-endothelium dependent dilatation (NID) had no change.</p

Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

Quantification of Circulating Endothelial Progenitor Cells Using the Modified ISHAGE Protocol

Circulating endothelial progenitor cells (EPC), involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data.In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS)), EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45(dim)CD34(+) cells were quantified for KDR. A minimum of 100 CD34(+) events were collected. For comparison, CD45(+)CD34(+) and CD45(-)CD34(+) were analysed simultaneously. The number of CD45(dim)CD34(+)KDR(+) cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend). An inverse correlation of CD45(dim)CD34(+)KDR(+) with disease activity (r = -0.475, p<0.001) was confirmed. Only CD45(dim)CD34(+)KDR(+) correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005). In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45(dim)CD34(+)KDR(+) EPC (p<0.05). CD45(+)CD34(+)KDR(+) and CD45(-)CD34(+)KDR(+) were indifferent between the three groups.Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration confirming previous findings with respect to the correlation of EPC with disease activity and the increase of EPC during statin therapy. The data of this study show the CD45(dim) fraction to harbour EPC

Assessment of endothelial function by brachial artery flow mediated dilatation in microvascular disease

<p>Abstract</p> <p>Background</p> <p>Cardiac syndrome X is an important therapeutic and diagnostic challenge to physician. Study of Csx patients may help to understand the pathophysiology of coronary microcirculation and to gain an insight on the management of these group patients.</p> <p>Methods</p> <p>We measured the flow mediated dilation of the brachial artery both endothelium dependent and independent vasodilatation by high resolution ultrasound in 30 cardiac syndrome X patients and matched with 30 healthy control subjects.</p> <p>Results</p> <p>Significantly decreased flow mediated dilatation was observed in patients when compared to control (9.42 ± 7.20 vs 21.11 ± 9.16 p < 0.01) but no significant difference was observed between groups in response to nitroglycerin (25.39 ± 6.82 vs 28.87 ± 8.69). Receiver operator characteristic analysis showed that value of < 11.11 had sensitivity of 80%, specificity 86.67%, positive predictive value 76.66%, negative predictive value 83.33%. In total, 46% of subjects had endothelial dysfunction and of them, CSX subjects had higher prevalence (76% vs 16% p < 0.01) than control subjects. Higher mean values of body mass index, systolic blood pressure and diastolic blood pressure was observed in subjects with FMD < 11.11 than > 11.11(p < 0.01). In logistic regression analysis, FMD was significantly associated with systolic blood pressure (Odds ratio 1.122 95% CI 1.053-1.196 p < 0.01) and body mass index (Odds 1.248 95%CI 0.995-1.56 p < 0.05).</p> <p>Conclusions</p> <p>The study suggests impairment of endothelial function in cardiac syndrome X patients. Increased Systolic blood pressure and body mass index may increase the risk of impairment of endothelial function in this group of patients.</p