Margarita Braunagel

Publications of Margarita Braunagel

• L-carnosine inhibits high-glucose-mediated matrix accumulation in human mesangial cells by interfering with TGF-β production and signalling.

  Authors: Hannes Köppel, Eva Riedl, Margarita Braunagel, Sibylle Sauerhoefer, Sabrina Ehnert, Patricio Godoy, Paula Sternik, Steven Dooley, Benito A Yard

  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 07/2011; 26(12):3852-8.

  Transforming growth factor beta is recognized as a major cytokine in extracellular matrix (ECM) pathobiology as occurs in diabetic nephropathy. While experimental studies have advanced a protectiveTransforming growth factor beta is recognized as a major cytokine in extracellular matrix (ECM) pathobiology as occurs in diabetic nephropathy. While experimental studies have advanced a protective role of carnosine for diabetic complications, a link between carnosine, TGF-β and matrix accumulation remains to be elucidated. In the present study, we tested the hypothesis that L-carnosine inhibits TGF-β production and signalling, thereby reducing hyperglycaemia-associated ECM accumulation. Human mesangial cells (MC) were cultured in high-glucose (HG, 25 mM D-glucose) medium alone or in HG medium to which 20 mM L-carnosine was added. Collagen VI (Col6) and fibronectin (FN) deposition and messenger RNA expression were studied. In addition, TGF-β production and activation of Smad1/5/8 (ALK1) and Smad2/3 (ALK5) pathways were assessed. Under HG conditions, deposition of Col6 and FN were increased 1.4- and 1.6-fold. This was significantly inhibited on the protein and messenger RNA level by L-carnosine. TGF-β production increased under HG conditions but was completely normalized by addition of L-carnosine. Addition of exogenous TGF-β could not overcome the effect of L-carnosine on Col6 and FN expression, indicating additionally interference with TGF-β downstream signalling. Along the same line, L-carnosine reduced TGF-β-mediated Smad2 phosphorylation, suggesting an inhibitory effect on ALK5 signalling. ALK1 signalling remained unchanged. Under HG conditions, pharmacologic inhibition of ALK5 prevented Col6 accumulation but did not change FN deposition. L-carnosine can modulate matrix accumulation in two ways. Firstly, inhibition of TGF-β production might result in an overall inhibition of matrix accumulation and secondly, L-carnosine inhibits TGF-β-induced matrix accumulation, most likely via inhibition of the ALK5 pathway.

• Optimization of contrast material delivery for dual-energy computed tomography pulmonary angiography in patients with suspected pulmonary embolism.

  Authors: John W Nance, Thomas Henzler, Mathias Meyer, Paul Apfaltrer, Margarita Braunagel, Radko Krissak, Uwe J Schoepf, Stefan O Schoenberg, Christian Fink

  Investigative radiology. 05/2011; 47(1):78-84.

  To prospectively compare subjective and objective measures of image quality using 4 different contrast material injection protocols in dual-energy computed tomography pulmonary angiography (CTPA)To prospectively compare subjective and objective measures of image quality using 4 different contrast material injection protocols in dual-energy computed tomography pulmonary angiography (CTPA) studies of patients with suspected pulmonary embolism. A total of 100 consecutive patients referred for CTPA for the exclusion of pulmonary embolism were randomized into 1 of 4 contrast material injection protocols manipulating iodine concentration and iodine delivery rate (IDR, expressed as grams of iodine per second): Iomeprol 400 at 3 mL/s (IDR = 1.2 gI/s), iomeprol 400 at 4 mL/s (IDR = 1.6 gI/s), iomeprol 300 at 5.4 mL/s (IDR = 1.6 gI/s), or iomeprol 300 at 4 mL/s (IDR = 1.2 gI/s). Total iodine delivery was held constant. Dual-energy CTPA of the lungs were acquired and used to calculate virtual 120 kV CTPA images as well as iodine perfusion maps. Attenuation values in the thoracic vasculature and image quality of virtual 120 kV CTPAs were compared between groups. Iodine perfusion maps were also compared by identifying differences in the extent of beam-hardening artifacts and subjective image quality. Protocols with an IDR of 1.6 gI/s provided the best attenuation profiles. CTPA image quality was greatest in the high concentration, high IDR (1.6 gI/s) protocol (P < 0.05 for all group comparisons) with no differences between the other groups (all P ≥ 0.05). Extent of beam-hardening artifacts and perfusion map image quality was significantly better using the high concentration, high IDR protocol as compared with all groups (P < 0.05 for all comparisons) and significantly worse using the low concentration, low IDR protocol as compared with all groups (all P ≥ 0.05); no difference was found between the high concentration, low IDR protocol and the low concentration, high IDR protocol (P = 0.73 for comparison of beam-hardening artifacts; P = 0.50 for comparison of perfusion map image quality). High iodine concentration and high IDR contrast material delivery protocols provide the best image quality of both CTPA and perfusion map images of the lung through high attenuation in the pulmonary arteries and minimization of beam-hardening artifacts.

• Carnosine prevents apoptosis of glomerular cells and podocyte loss in STZ diabetic rats.

  Authors: Eva Riedl, Frederick Pfister, Margarita Braunagel, Paul Brinkkötter, Paula Sternik, Martina Deinzer, Stephan J L Bakker, Rob H Henning, Jacob van den Born, Bernhard K Krämer, Gerjan Navis, Hans-Peter Hammes, Benito Yard, Hannes Koeppel

  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 01/2011; 28(2):279-88.

  We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study,We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study, we hypothesized that carnosine administration to diabetic rats might protect the kidneys from glomerular apoptosis and podocyte loss. We examined the effect of oral L-carnosine administration (1g/kg BW per day) on apoptosis, podocyte loss, oxidative stress, AGEs and hexosamine pathway in kidneys of streptozotocin-induced diabetic Wistar rats after 3 months of diabetes and treatment. Hyperglycemia significantly reduced endogenous kidney carnosine levels. In parallel, podocyte numbers significantly decreased (-21% compared to non-diabetics, p<0.05), apoptotic glomerular cells numbers increased (32%, compared to non-diabetic, p<0.05) and protein levels of bax and cytochrome c increased (175% and 117%). Carnosine treatment restored carnosine kidney levels, prevented podocytes loss (+23% compared to diabetic, p<0.05), restrained glomerular apoptosis (-34% compared to diabetic; p<0.05) and reduced expression of bax and cytochrome c (-63% and -54% compared to diabetics, both p<0.05). In kidneys of all diabetic animals, levels of ROS, AGEs and GlcNAc-modified proteins were increased. By inhibition of pro-apoptotic signaling and independent of biochemical abnormalities, carnosine protects diabetic rat kidneys from apoptosis and podocyte loss.