Emerging Role of Galectin-3 in Pulmonary Artery Hypertension

Pulmonary arterial hypertension (PAH) is multifactorial disadptive disease with poor clinical outcomes associated with increased pulmonary artery pressure resulting in primary small-to-moderate pulmonary artery remodeling. Numerous factors, including smooth muscle cell proliferation, vasospasm, vascular fibrosis and occlusion, direct vascular injury and inflammation, impaired repair of vasculature, are involved in the pathogenesis of PAH. It has been suggested that galectin-3 as a biomarker of excessive fibrosis and inflammation can be useful predictor of both severity and prognosis in patient with PAH. The short communication is reported that elevated Gal-3 levels were found in majority patients with PAH depending on clinical status and of the disease. Although elevated Gal-3 levels were associated with a higher risk of all-cause mortality, cardiovascular mortality, and right ventricle heart failure, the value of this biomarker in PAH patients at high risk stratification is uncertain and requires to be investigated in large clinical trials

Endogenous vascular repair system in cardiovascular disease: The role of endothelial progenitor cells

BackgroundCardiovascular (CV) disease has been considered as the first global leading cause of premature death in last decades. Vascular complications close correspond to development of endothelial dysfunction, microvascular inflammation, accelerating atherosclerosis, coagulopathy, and thrombosis, in pathogenesis of which altered vascular reparation is core player and possible target for further treatment strategy.AimsThe aim of the review is: to summarize knowledge regarding the role of endothelial progenitor cells (EPCs) as a core component of endogenous vascular repair system in CV disease.MethodsThis is a descriptive review based on evidence of pre-clinical and clinical studies published within last decade.ResultsThe review is reported that developing of CV disease associates with lowered number and impaired function of circulating EPCs, which play a pivotal role in endogenous reparation of vasculature and restore endothelial function after various injuries on the vessels. EPCs could be modified by several stimuli including epigenetic factors and thereby they are failed completely restoring vascular structure and endothelial function. However, there is unclear whether EPC dysfunction is just a whiteness of the evolution of CV disease or it could be a trigger of CV disease manifestation in the vulnerable population.ConclusionEPCs are novel biological marker of impaired vascular reparation and CV risk with predictive value. Large clinical trials are required to justify number and function of EPCs as independent prognosticator of CV risk

Predictive Value of Circulating SPARC-Related protein Osteonectin in Patients with Symptomatic Moderate-to-Severe Ischemic-Induced Chronic Heart Failure

Aim: To evaluate the prognostic value of circulating osteonectin for cumulative survival and hospitalization in patients with ischemic chronic heart failure (CHF).Methods: One hundred fifty four patients with ischemic symptomatic moderate-to-severe CHF were prospectively enrolled at discharge from the hospital. Observation period was up to 3 years (156 weeks). Blood samples for hematology, chemistry, and biomarker measurements were collected at baseline prior to study entry. ELISA method for measurement of circulating osteonectin (OSN) was used.Results: During a median follow-up of 2.18 years we identified 21 deaths and 106 readmissions. Medians of circulating levels of OSN in survivors patient and subjects who died were 670.96 ng/mL (95% confidence interval [CI] = 636.53-705.35 ng/mL) and 907.84 ng/mL (95% CI = 878.02-937.60 ng/mL). Receive Operation Characteristic curve analysis has shown the best balanced cutoff point of OSN concentration for cumulative survival equal 845.15 ng/mL. A significantly divergence of Kaplan-Meier survival curves constructed for patients with high (> 845.15 ng/mL) and low (<845.15 ng/mL) concentrations of OSN was found. Circulating OSN independently predicted all-cause mortality (OR = 1.23; 95% CI = 1.10–1.36; P < 0.001), CHF-related death (OR = 1.46; 95% CI 1.22–1.80; P < 0.001), and also CHF-related readmission (OR = 1.92; 95% CI = 1.77 – 2.45; P<0.001) within 3 year of follow-up period.Conclusion: Increased circulating SPARC family member OSN associates with increased 3-year CHF-related death, all-cause mortality, and risk for readmission due to CHF

Predictive value of apoptotic microparticles to mononuclear progenitor cells ratio in advanced chronic heart failure patients

AbstractBackgroundAcutely decompensated chronic heart failure (ADHF) is considered a life-threatening event. Despite contemporary treatment strategies of ADHF, frequent recurrent hospitalizations due to other cardiovascular reasons after discharge of patients from hospital occur. The objective of the study was to examine the prognostic value of circulating endothelial-derived apoptotic microparticles (EMPs) to mononuclear progenitor cells (MPCs) ratio for post-discharge patients with clinical stabilization after ischemic ADHF.MethodsWe consecutively enrolled 136 patients (62 male) with coronary artery disease (CAD) admitted with a primary diagnosis of ADHF. All patients gave written informed consent for participation in the study. At baseline, all enrolled patients were hemodynamically stable and they had New York Heart Association (NYHA) III/IV classes of ischemic chronic heart failure (CHF). Observation period started at discharge from the hospital and was up to 3 years. Flow cytometry analysis for quantifying the number of EMPs and angiogenic MPCs was used.ResultsCalculated EMP to MPC ratios in survivor and dead patient cohort were 8.4 (95% CI=7.6–9.2) and 78.9 (95% CI=53.0–116.6), respectively (p=0.001). MPCs, EMPs, NYHA class, N-terminal pro-brain natriuretic peptide (NT-proBNP) and increased NT-proBNP>30% within 24–84h of admission period remained statistically significant for all-cause mortality, CHF-related death, and CHF-related rehospitalization, whereas left ventricular ejection fraction and high-sensitivity C-reactive protein for all variables did not. We found that the addition of EPMs to MPCs ratio to the ABC model (NT-pro-BNP, increased NT-pro-BNP>30%) improved the relative integrated discrimination indices by 19.6% for all-cause mortality, by 21.7% for CHF-related death, and by 19.5% for CHF-related rehospitalization.ConclusionWe demonstrated that EMP to MPC ratio is considered an important indicator of an imbalance between angiogenic and apoptotic responses with possible relation to cardiovascular outcomes in post-discharge patients with clinical stabilization after ischemic ADHF

Patching up the No-Boundary Proposal with virtual Euclidean wormholes

In quantum cosmology, one often considers tunneling phenomena which may have occurred in the early universe. Processes requiring quantum penetration of a potential barrier include black hole pair creation and the decay of vacuum domain walls. Ideally, one calculates the rates for such processes by finding an instanton, or Euclidean solution of the field equations, which interpolates between the initial and final states. In practice, however, it has become customary to calculate such amplitudes using the No-Boundary Proposal of Hartle and Hawking. A criticism of this method is that it does not use a single path which interpolates between the initial and final states, but two disjoint instantons: One divides the probability to create the final state from nothing by the probability to create the initial state from nothing and decrees the answer to be the rate of tunneling from the initial to the final state. Here, we demonstrate the validity of this approach by constructing continuous paths connecting the ingoing and outgoing data, which may be viewed as perturbations of the set of disconnected instantons. They are off-shell, but will still dominate the path integral as they have action arbitrarily close to the no-boundary action. In this picture, a virtual domain wall, or wormhole, is created and annihilated in such a way as to interface between the disjoint instantons. Decay rates calculated using our construction differ from decay rates calculated using the No-Boundary Proposal only in the prefactor; the exponent, which usually dominates the result, remains unchanged.Comment: 23 pages REVTeX plus 7 figure

Asymptotic Density of Eigenvalue Clusters for the Perturbed Landau Hamiltonian

We consider the Landau Hamiltonian (i.e. the 2D Schroedinger operator with constant magnetic field) perturbed by an electric potential V which decays sufficiently fast at infinity. The spectrum of the perturbed Hamiltonian consists of clusters of eigenvalues which accumulate to the Landau levels. Applying a suitable version of the anti-Wick quantization, we investigate the asymptotic distribution of the eigenvalues within a given cluster as the number of the cluster tends to infinity. We obtain an explicit description of the asymptotic density of the eigenvalues in terms of the Radon transform of the perturbation potential V.Comment: 30 pages. The explicit dependence on B and V in Theorem 1.6 (i) - (ii) indicated. Typos corrected. To appear in Communications in Mathematical Physic

Recycling universe

If the effective cosmological constant is non-zero, our observable universe may enter a stage of exponential expansion. In such case, regions of it may tunnel back to the false vacuum of an inflaton scalar field, and inflation with a high expansion rate may resume in those regions. An ``ideal'' eternal observer would then witness an infinite succession of cycles from false vacuum to true, and back. Within each cycle, the entire history of a hot universe would be replayed. If there were several minima of the inflaton potential, our ideal observer would visit each one of these minima with a frequency which depends on the shape of the potential. We generalize the formalism of stochastic inflation to analyze the global structure of the universe when this `recycling' process is taken into account.Comment: 43 pages, 10 figure

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8(+) T cells (CD44(hi)CD62L(hi)CCR7(+)). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8(+) T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8(+) central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung