Anichstr.

Innsbruck, Austria

Anichstr.

Innsbruck, Austria
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Theurl M.,Anichstr. | Schgoer W.,Anichstr. | Albrecht K.,Anichstr. | Jeschke J.,Innsbruck Medical University | And 11 more authors.
Circulation Research | Year: 2010

Rationale: The neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. Objective: Catestatin shares several functions with angiogenic factors. We therefore reasoned that catestatin induces growth of new blood vessels. Methods and Results: Catestatin induced migration, proliferation, and antiapoptosis in endothelial cells and exerted capillary tube formation in vitro in a Matrigel assay, and such effects were mediated via G protein, mitogen-activated protein kinase, and Akt. Catestatin-induced endothelial cell functions are further mediated by basic fibroblast growth factor, as shown by blockade of effects by a neutralizing fibroblast growth factor antibody. Furthermore, catestatin released basic fibroblast growth factor from endothelial cells and stimulated fibroblast growth factor signaling. In addition to its function on endothelial cells, catestatin also exerted effects on endothelial progenitor cells and vascular smooth muscle cells. In vivo, catestatin induced angiogenesis in the mouse cornea neovascularization assay and increased blood perfusion and number of capillaries in the hindlimb ischemia model. In addition to angiogenesis, catestatin increased density of arterioles/arteries and incorporation of endothelial progenitor cells in the hindlimb ischemia model, indicating induction of arteriogenesis and postnatal vasculogenesis. Conclusion: We conclude that catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism. © 2010 American Heart Association, Inc.


PubMed | Anichstr.
Type: Journal Article | Journal: Current neurovascular research | Year: 2013

A marker of Alzheimers disease (AD) with a high sensitivity and specificity would facilitate a diagnosis at early stages. Blood platelets may be of particular interest in search of biomarkers, because they express amyloid-precursor protein (APP), and display a dysfunctional processing in AD. The aim of the present study is to establish and validate an assay for secreted amyloid-precursor protein (sAPP)- and - in platelets of AD and mild cognitively impaired (MCI) subjects, compared to healthy young and old controls. Freshly isolated platelet extracts (25 g) were incubated with or without recombinant BACE1 (beta-site APP-Cleaving Enzyme; -secretase, 8U) at 37C and low pH and the levels of sAPP- and sAPP-b were measured by specific ELISAs. Our data show that sAPP- levels were not different between AD, MCI and control subjects. However, sAPP- levels in MCI and AD were significantly elevated relative to controls. When recombinant BACE1 was added, no changes were seen in sAPP- levels, but the processed sAPP- levels were again markedly increased. The sAPP- processing was specific and selective after 2.5 hours at 37C, and was possibly mediated by exogenous BACE1, because it was blocked by a BACE1 inhibitor and BACE1 enzyme levels were enhanced in AD patients. Our data reveal that quantitive analysis of platelet sAPP- assay by ELISA may be a novel diagnostic biomarker for MCI and AD.


PubMed | Anichstr.
Type: Journal Article | Journal: Current neurovascular research | Year: 2016

Pericytes are perivascular cells and have heterogenous roles in the brain, such as controlling blood flow and entry of immune cells or regulating the blood-brain barrier. Platelet-derived growth factor (PDGF) receptor-beta (PDGFR) is highly expressed in pericytes, representing the most selective biomarker. The aim of the present study was to culture primary mouse pericytes and to determine the expression pattern by Western Blot as well as immunostainings. We will study the effects of different exogenous stimuli (such as transforming growth factor- (TGF1), PDGF-BB, oxygendeprivation, beta-amyloid or serumfree conditions) on the different pericyte markers. Using Western Blot analyses, we show that PDGFR is selectively expressed in pericytes as a 160 kDa protein. Nestin, although not exclusively specific, is also expressed by pericytes, but markedly downregulated under serum-free conditions. PDGF-BB and oxygen-deprivation dramatically reduced PDGFR expression, while TGF1 increased its expression. The expression of PDGFR was intracellular as shown by confocal microscopy. Using Western Blot analyses, we demonstrate that pericytes also contain a 100 kDa PDGFR protein. However, in contrast to cortex brain slices, pericytes do not express a phosphorylated (Y740) isoform. Interestingly, PDGF-BB markedly reduced the 160 kDa isoform of PDGFR. In conclusion, our data show a detailed expression of different forms of PDGFR in primary pericytes, which is different to brain slices. However, we suggest that PDGFR is a highly selective marker for pericytes.


PubMed | Anichstr
Type: Journal Article | Journal: Gut | Year: 2011

Polymorphisms in NOD2, encoding an intracellular pattern recognition receptor, contribute the largest fraction of genetic risk for Crohns disease among the >40 risk loci identified so far. Autophagy plays a prominent role in the innate immune response towards intracellular bacteria. The discovery of the autophagy genes ATG16L1 and IRGM as risk factors for Crohns disease turned autophagy into the spotlight in inflammatory bowel disease (IBD). Remarkably, NOD2 has recently been identified as a potent autophagy inducer. A physical interaction of NOD2 and ATG16L1 appears to be required for autophagic clearance of intracellular pathogens. Moreover, Crohns disease-associated NOD2 and ATG16L1 variants exhibit a defect in the induction of an autophagic response and hence predict autophagy as a key converging mechanism that leads to Crohns disease. Another pathway that is closely intertwined with autophagy and mutually cross-regulated is the unfolded protein response (UPR), which is induced by endoplasmic reticulum (ER) stress. Genes involved in the UPR (XBP1, ORMDL3) have also been genetically associated with Crohns disease and ulcerative colitis. Moreover, the intestinal epithelium at the interface between host and microbe appears particularly affected by IBD-associated hypomorphic function of autophagy and the UPR. The functional convergence of main genetic risk factors for IBD on these innate immune pathways has hence important implications for the hosts interaction with the microbiota. Moreover, the genetic convergence on these molecular mechanisms may open novel therapeutic options for IBD that deserve further exploration.

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