Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) affects milions of people and can result in myocardial infarction (MI). Previously, mast cells (MC) have been extensively investigated in the context of hypersensitivity, however as regulators of the local inflammatory response they can potentially contribute to CAD and/or its progression. The aim of the study was to assess if serum concentration of MC proteases: carboxypeptidase A3, cathepsin G and chymase 1 is associated with the extension of CAD and MI. METHODS: The 44 patients with angiographically confirmed CAD (23 subjects with non-ST-segment elevation MI [NSTEMI] and 21 with stable CAD) were analyzed. Clinical data were obtained as well serum concentrations of carboxypeptidase A3, cathepsin G and chymase 1 were also measured. RESULTS: Patients with single vessel CAD had higher serum concentration of carboxypeptidase than those with more advanced CAD (3838.6 ± 1083.1 pg/mL vs. 2715.6 ± 442.5 pg/mL; p = 0.02). There were no significant differences in levels of any protease between patients with stable CAD and those with NSTEMI. Patients with hypertension had ≈2-fold lower serum levels of cathepsin G than normotensive individuals (4.6 ± 0.9 pg/mL vs. 9.4 ± 5.8 pg/mL; p = 0.001). Cathepsin G levels were also decreased in sera of the current smokers as compared with non-smokers (3.1 ± 1.2 ng/mL vs. 5.8 ± 1.2 ng/mL, p = 0.02). CONCLUSIONS: Decreased serum level of carboxypeptidase is a hallmark of more advanced CAD. Lower serum levels of carboxypeptidase A3 and catepsin G are associated with risk factors of blood vessel damage suggesting a protective role of these enzymes in CAD.

Heat shock proteins (HSPs) in the homeostasis of regulatory T cells (Tregs).

Heat shock proteins (HSPs) belong to the family of conservative polypeptides with a high homology of the primary structure. The uniqueness of this family lies in their ability to interact with a large number of different proteins and provide protection from cellular and environmental stress factors as molecular chaperones to keep protein homeostasis. While intracellular HSPs play a mainly protective role, extracellular or membrane-bound HSPs mediate immunological functions and immunomodulatory activity. In immune system are subsets of cells including regulatory T cells (Tregs) with suppressive functions. HSPs are implicated in the function of innate and adaptive immune systems, stimulate T lymphocyte proliferation and immunomodulatory functions, increase the effectiveness of cross-presentation of antigens, and induce the secretion of cytokines. HSPs are also important in the induction, proliferation, suppressive function, and cytokine production of Tregs, which are a subset of CD4+ T cells maintaining peripheral tolerance. Together HSPs and Tregs are potential tools for future clinical interventions in autoimmune disease.

Elevated Serum Tryptase and Endothelin in Patients with ST Segment Elevation Myocardial Infarction: Preliminary Report.

UNLABELLED: An inflammatory response plays a crucial role in myocardial damage after an acute myocardial infarction. OBJECTIVES: To measure serum concentrations of several mediators in patients with an acute myocardial infarction (STEMI) and to assess their potential relationship with a risk of coronary instability. PATIENTS AND METHODS: The 33 patients with STEMI and 19 healthy volunteers were analyzed. The clinical data were obtained; as well serum concentrations of tryptase, endothelin (ET-1), angiogenin, soluble c-kit, and PDGF were measured. RESULTS: Patients with STEMI had higher serum tryptase and ET-1 than healthy volunteers (2,5 ± 0,4 ng/mL versus 1,1 ± 0,4 ng/mL and 0,7 ± 0,1 ng/mL versus 0,3 ± 0,1 ng/mL, resp.). Subjects with significant lesion in left anterior descending artery (LAD) had lower serum ET-1 compared to those with normal LAD (0,6 ± 0,2 pg/mL versus 0,9 ± 0,4 pg/mL). Patients with three-vessel coronary artery disease (CAD) had higher level of soluble c-kit compared to those with one- or two-vessel CAD: 19,9 ± 24,1 ng/mL versus 5,6 ± 1,9 ng/mL. CONCLUSIONS: Elevated serum tryptase and ET-1 may be markers of increased coronary instability; some cytokines may be related to the extension of CAD.

Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus Anti-Angiogenic Factors.

OBJECTIVE: Hypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease. It has been reported recently that hypertensive patients and animals are characterized by decreased density of arterioles and capillaries in the tissues, called rarefaction. Rarefaction significantly increases peripheral resistance which results in elevated blood pressure, leads to vessel damage and induction of inflammation. Therefore, we hypothesized that hypertension is associated with decreased serum concentration of physiological pro-angiogenic factors and concomitant increased production of angiogenesis inhibitors. MATERIALS AND METHODS: 82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to measure serum levels of the following cytokines: endostatin, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF). RESULTS: Hypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. In addition, hypertension was associated with decreased levels of physiological pro-angiogenic mediators such as: angiogenin and bFGF. The hypertensive group was also characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of inflammation. CONCLUSIONS: Presented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation.

Taxonomic position and phylogeny of the genus Vargasiella (Orchidaceae, Vandoideae) based on molecular and morphological evidence.

Since the description of the Neotropical genus Vargasiella in 1952, its taxonomic position has remained unclear, mainly due to a lack of sufficient data. In this study, the taxonomic position of Vargasiella was revised based on the outcomes of macro- and micromorphological studies, analyses of selected molecular markers and ecological methods of niche distribution modeling. The phylogenetic relationships were inferred using three DNA markers: matK, trnL-F and ITS sequences. The morphological studies included the analysis of macromorphological features of herbarium specimens as well as micromorphological examination of preserved flowers. The ecological niche modeling was applied to identify the distribution of the suitable niches of the studied taxa. The relationships between Vargasiella and most similar taxa remain unresolved based on the molecular analysis. The outcomes from the morphological studies indicated significant differences between Vargasiella, Warrea and Warreopsis. Moreover, a niche shift in response to changing climate after the last glacial maximum is observed in Vargasiella, while no substantial changes in the occupied habitats were identified in the other related taxa. The clocktree of the Zygopetaleae estimated from the matK gene indicated that the most recent common ancestors of Vargasiella, Warrea and Warreopsis originated in the Miocene, while the divergence time for Vargasiella and Warrea was assessed at approximately 5.4 Ma ago. Vargasiella seems to be an outshoot of the main branch of evolution of the Zygopetaleae. It is noteworthy that the Vargasiella-Warrea dichotomy could have taken place later than the divergence of Warreopsis from the mutual lineage. The molecular analysis and morphological data suggest that Vargasiella and Warrea could have evolved from a common ancestor. Accumulation of morphological differences and acceleration of the evolution of Vargasiella were more intensive than in other Warreinae and this could probably be synchronized with adaptation to different climatic conditions.