Work group of Prof. Lendeckel

Another focus of the working group is the elucidation of the function of the ectopeptidase membrane alanyl aminopeptidase (EC3.4.11.2, CD13, APN) for the pathogenesis of cardiovascular, autoimmune and inflammatory diseases, diabetes and tumors. The priority objective of current projects is the elucidation of the molecular mechanisms underlying the effects resulting from the “knock-out” or the pharmacological inhibition of APN / CD13. These effects include:

• Anti-inflammatory, immunomodulatory effect (e.g. in autoimmune diseases)

• Dysregulation of components of the Wnt signaling pathway

• Inhibition of angiogenesis and tumor growth (overcoming resistance to chemotherapeutic agents, effect on tumor stem cells)

• Modulation of proliferation and differentiation of immune, tumor, progenitor cells)

• Shift of macrophages / microglia differentiation from M1 to M2

The Renin Angiotensin System (RAS) is associated with glucose homeostasis in a number of ways. The activation of the RAS and the resulting increased plasma concentrations of AngII cause insulin resistance in muscle and adipose tissue. In addition to the induction of insulin resistance, the effect of increased AngII levels is also associated with the impairment of the β-cell function and thus the adequate production / secretion of insulin.

Beneficial effects of the alternative RAS axis ACE2 / Ang- (1-7) / Mas with regard to glucose homeostasis are described, but mainly relate to the improvement of insulin sensitivity and thus glucose uptake in peripheral tissue (muscle, adipose tissue). We have already been able to show that Ang-(1-7) also increases glucose-stimulated insulin secretion (GSIS) (Sahr et al.).

As part of a project funded by the DFG (Le/13-1), the responsible receptors (Mas and / or MrgD) are now to be identified and, in addition, the extent to which Ang- (1-7) and / or related agonists represent a new and very promising strategy for the treatment of diabetes mellitus, in that, in addition to improving the peripheral insulin resistance, they also restore the-cell-associated function, namely the adequate GSIS by stimulating the regeneration of functional β cells.

• Wolke C, Antileo E, Lendeckel U. WNT signaling in atrial fibrillation. Exp Biol Med (Maywood). 2021 May;246(9):1112-1120.
• Schild L, Döring M, Jansing S, Peter D, Jagirdar G, Wolke C, Gardemann A, Lendeckel U. Proliferation of C6 glioma cells requires the phospholipid remodeling enzyme tafazzin independent of cardiolipin composition. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Mar;1865(3):158596.
• Gürtler S, Wolke C, Otto O, Heise N, Scholz F, Laporte A, Elsner M, Jörns A, Weinert S, Döring M, Jansing S, Gardemann A, Lendeckel U, Schild L. Tafazzin-dependent cardiolipin composition in C6 glioma cells correlates with changes in mitochondrial and cellular functions, and cellular proliferation. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):452-465.        
• Ohlig T, Lea DV, Gardemann A, Wolke C, Gürtler S, Peter D, Schild L, Lendeckel U. Effects of siRNA-dependent knock-down of cardiolipin synthase and tafazzin on mitochondria and proliferation of glioma cells. BBA - Molecular and Cell Biology of Lipids, 2018;1863(4):379-387.
• Lendeckel U and Wolke C.; Structuring (right) atrial fibrillation: location matters. Europace 2018;20(6):906-907.
• Bukowska A, Spiller L, Wolke C, Lendeckel U, Weinert S, Hoffmann J, Bornfleth P, Kutschka I, Gardemann A, Isermann B, and Goette A.; Protective regulation of the ACE2/ACE gene expression by oestrogen in human atrial tissue from elderly men. Exp Biol Med (Maywood). 2017;242(14):1412-1423.
• Wolke C, Teumer A, Endlich K, Endlich N, Rettig R, Stracke S, Fiene B, Aymanns S, Felix SB, Hannemann A, Lendeckel U.; Serum Protease Activity in Chronic Kidney Disease Patients ˗ The GANI_MED Renal Cohort. Exp Biol Med (Maywood). 2017;242(5):554-563.
• Schild L, Mürke E, Stoll S, Lendeckel U, Reinhold D. The mitochondrial phospholipid cardiolipin is involved in the regulation of T-cell proliferation. BBA - Molecular and Cell Biology of Lipids, 2016;1861:748-754.
• Sahr A, Wolke C, Maczewsky J, Krippeit-Drews P, Tetzner A, Drews G, Venz S, Gürtler S, van den Brandt J, Berg S, Döring P, Dombrowski F, Walther T, Lendeckel U.; The Angiotensin-(1-7)/Mas axis improves pancreatic β-cell function in vitro and in vivo. Endocrinology. 2016;157(12):4677-4690.
• Chilukoti RK, Giese A, Malenke W, Homuth G, Bukowska A, Goette A, Felix SB, Kanaan J, Wollert HG, Evert K, Verheule S, Jais P, Hatem SN, Lendeckel U, Wolke C.; Atrial fibrillation and rapid acute pacing regulate adipocyte/adipositas-related gene expression in the atria. Int J Cardiol. 2015;187:604-13.
• Wolke C, Bukowska A, Goette A, Lendeckel U.; Redox control of cardiac remodeling in atrial fibrillation. Biochim Biophys Acta. 2015;1850(8):1555-65.
• Härdtner C, Mörke C, Walther R, Wolke C, Lendeckel U. High glucose activates the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β-cells. Int J Mol Med. 2013 Oct;32(4):795-804.