Biomedical subjects

Christian Scheler

Publications and source records attributed to Christian Scheler.

4 recordsLinked to original sources

PubMed2005

Myocardial preconditioning and remote renal preconditioning--identifying a protective factor using proteomic methods?

It is still unknown whether remote ischemic preconditioning is mediated by a humoral or a neurogenic mechanism from the preconditioning to the preconditioned tissue. The purpose of the following study was to identify a possible humoral trigger of ischemic myocardial preconditioning and remote renal preconditioning. Open chest rats were subjected to a coronary artery occlusion period of 45 min followed by 2 h of reperfusion (Control animals; n = 6). The coronary preconditioned group (IPC, n = 6) was subjected to a preceding preconditioning period of 5 min coronary artery occlusion followed by 5 min of reperfusion, repeated three times. The renal preconditioned group (IPR, n = 6) was subjected to a preceding renal artery occlusion period of 10 min followed by 20 min of reperfusion. Area at risk (AAR) and infarcted area (IA) were determined at the end of each protocol. Blood samples were taken at the end of the preconditioning protocols from parallel experiments for proteomic analysis using two-dimensional gel electrophoresis (2-DE), matrix assisted laser desorption and ionization-time of flight-mass spectrometry (MALDI-TOF-MS), and liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS). IA/AAR was 87.8 +/- 10.7% in the control group. IPC and IPR significantly reduced IA/AAR (58.2 +/- 9.3% and 56.9 +/- 9.0%, p < 0.001). Proteomic analyses detected four protein spots which were either up- (n = 3) or down-regulated in the preconditioned groups vs. the control group. The three up-regulated protein spots were identified as albumin fragments, whereas the down-regulated spot was identified as liver regeneration-related protein (LRRG03). Interestingly, albumin modification by brief ischemia has been recently shown and evaluated for the clinical diagnosis of sublethal myocardial ischemia. However, no differentially abundant proteins which possess a known signaling function could be found. Hence, though there is a differential protein expression in blood following IPC and IPR, our data are not in favor of a humoral mediator of remote preconditioning with a molecular weight of more than 8 kDa. Our results rather suggest either a neurogenic pathway or a mediator smaller than 8 kDa.

Albumins↗

PubMed2004

Elevated fluid shear stress enhances postocclusive collateral artery growth and gene expression in the pig hind limb.

OBJECTIVE: The role of fluid shear stress (FSS) in collateral vessel growth remains disputed and prospective in vivo experiments to test its morphogenic power are rare. Therefore, we studied the influence of FSS on arteriogenesis in a new model with extremely high levels of collateral flow and FSS in pig and rabbit hind limbs. METHODS AND RESULTS: A side-to-side anastomosis was created between the distal stump of one of the bilaterally occluded femoral arteries with the accompanying vein. This clamps the collateral reentry pressure at venous levels and increases collateral flow, which is directed to a large part into the venous system. This decreases circumferential wall stress and markedly increases FSS. One week after anastomosis, angiographic number and size of collaterals were significantly increased. Maximal collateral flow exceeded by 2.3-fold that obtained in the ligature-only hind limb. Capillary density increased in lower leg muscles. Immunohistochemistry revealed augmented proliferative activity of endothelial and smooth muscle cells. Intercellular adhesion molecule-1 and vascular cell adhesion molecule (VCAM)-1 were upregulated, and monocyte invasion was markedly increased. In 2-dimensional gels, actin-regulating cofilin1 and cofilin2, destrin, and transgelin2 showed the highest degree of differential regulation. CONCLUSIONS: High levels of FSS cause a strong arteriogenic response, reinstate cellular proliferation, stimulate cytoskeletal rearrangement, and normalize maximal conductance. FSS is the initiating molding force in arteriogenesis. The role of fluid shear stress on the development of a collateral circulation was studied by abruptly increasing collateral blood flow by a distal femoral artery-to-vein anastomosis. This increased number and size of collateral vessels to a hitherto unknown degree. Fluid shear stress is the primary and strongest arteriogenic stimulus.

Actin Depolymerizing Factors↗

PubMed2003

Structural changes in plasma circulating fibrinogen after moderate beer consumption as determined by electrophoresis and spectroscopy.

The effects of short-term moderate beer consumption (MBC) on plasma circulating fibrinogen (PCF) in patients suffering from coronary atherosclerosis were investigated by use of 2-dimensional electrophoresis (2-DE), circular dichroism (CD), and Fourier transform infrared spectroscopy (FT-IR). Forty-eight volunteers after coronary bypass surgery were divided into experimental (EG) and control (CG) groups, each of 24. Patients of the EG group consumed 330 mL of beer/day (about 20 g of alcohol) for 30 consecutive days, and CG volunteers drank mineral water instead of beer. Blood samples were collected before and after the experiment. In 21 out of 24 patients after beer consumption the plasma circulating fibrinogen was compromised: changes in its secondary structure were found. These changes were expressed in relatively low electrophoretic mobility and charge heterogeneity, decrease in alpha-helix and increase in beta-sheet, and in slight shift of amide I and II bands. Our findings indicate that one of the positive benefits of moderate beer consumption is to diminish the production of fibrinogen and its stability, which reduces the potential risk exerted by this protein. Thus, in most of beer-consuming patients some qualitative structural changes in plasma circulating fibrinogen were detected.

Aged↗

PubMed2002

An iterative calibration method with prediction of post-translational modifications for the construction of a two-dimensional electrophoresis database of mouse mammary gland proteins.

Protein databases serve as general reference resources providing an orientation on two-dimensional electrophoresis (2-DE) patterns of interest. The intention behind constructing a 2-DE database of the water soluble proteins from wild-type mouse mammary gland tissue was to create a reference before going on to investigate cancer-associated protein variations. This database shall be deemed to be a model system for mouse tissue, which is open for transgenic or knockout experiments. Proteins were separated and characterized in terms of their molecular weight (M(r)) and isoelectric point (pI) by high resolution 2-DE. The proteins were identified using prevalent proteomics methods. One method was peptide mass fingerprinting by matrix-assisted laser desorption/ionization-mass spectrometry. Another method was N-terminal sequencing by Edman degradation. By N-terminal sequencing M(r) and pI values were specified more accurately and so the calibration of the master gel was obtained more systematically and exactly. This permits the prediction of possible post-translational modifications of some proteins. The mouse mammary gland 2-DE protein database created presently contains 66 identified protein spots, which are clickable on the gel pattern. This relational database is accessible on the WWW under the URL: http://www.mpiib-berlin.mpg.de/2D-PAGE.

Animals↗