@misc{BiterovaEsmaeeliMoghaddamTabalvandaniAlanenetal.2018,
  author    = {Biterova, Ekaterina and Esmaeeli Moghaddam Tabalvandani, Mariam and Alanen, Heli I. and Saaranen, Mirva and Ruddock, Lloyd W.},
  title     = {Structures of Angptl3 and Angptl4},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1048},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-46794},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-467943},
  pages     = {14},
  year      = {2018},
  abstract  = {Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34\% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.},
  language  = {en}
}
@misc{HoffmannKretschmerLawrenzetal.2015,
  author    = {Hoffmann, Linda Sarah and Kretschmer, Axel and Lawrenz, Bettina and Hocher, Berthold and Stasch, Johannes-Peter},
  title     = {Chronic activation of heme free Guanylate Cyclase leads to renal protection in Dahl salt-sensitive rats},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch naturwissenschaftliche Reihe},
  number    = {489},
  issn      = {1866-8372},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-408088},
  pages     = {17},
  year      = {2015},
  abstract  = {The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectively activate the heme free form of sGC and target the disease associated enzyme. In this study, a therapeutic effect of long-term activation of heme free sGC by the sGC activator cinaciguat was investigated in an experimental model of salt-sensitive hypertension, a condition that is associated with increased oxidative stress, heme loss from sGC and development of chronic renal failure. For that purpose Dahl/ss rats, which develop severe hypertension upon high salt intake, were fed a high salt diet (8\% NaCl) containing either placebo or cinaciguat for 21 weeks. Cinaciguat markedly improved survival and ameliorated the salt-induced increase in blood pressure upon treatment with cinaciguat compared to placebo. Renal function was significantly improved in the cinaciguat group compared to the placebo group as indicated by a significantly improved glomerular filtration rate and reduced urinary protein excretion. This was due to anti-fibrotic and antiinflammatory effects of the cinaciguat treatment. Taken together, this is the first study showing that long-term activation of heme free sGC leads to renal protection in an experimental model of hypertension and chronic kidney disease. These results underline the promising potential of cinaciguat to treat renal diseases by targeting the disease associated heme free form of sGC.},
  language  = {en}
}