@article{ShityakovHayashiStoerketal.2021,
  author    = {Shityakov, Sergey and Hayashi, Kentaro and St{\"o}rk, Stefan and Scheper, Verena and Lenarz, Thomas and F{\"o}rster, Carola Y.},
  title     = {The conspicuous link between ear, brain and heart - Could neurotrophin-treatment of age-related hearing loss help prevent Alzheimer's disease and associated amyloid cardiomyopathy?},
  series = {Biomolecules},
  volume    = {11},
  journal   = {Biomolecules},
  number    = {6},
  issn      = {2218-273X},
  doi       = {10.3390/biom11060900},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241084},
  year      = {2021},
  abstract  = {Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction and cognitive decline. While the deposition of amyloid β peptide (Aβ) and the formation of neurofibrillary tangles (NFTs) are the pathological hallmarks of AD-affected brains, the majority of cases exhibits a combination of comorbidities that ultimately lead to multi-organ failure. Of particular interest, it can be demonstrated that Aβ pathology is present in the hearts of patients with AD, while the formation of NFT in the auditory system can be detected much earlier than the onset of symptoms. Progressive hearing impairment may beget social isolation and accelerate cognitive decline and increase the risk of developing dementia. The current review discusses the concept of a brain-ear-heart axis by which Aβ and NFT inhibition could be achieved through targeted supplementation of neurotrophic factors to the cochlea and the brain. Such amyloid inhibition might also indirectly affect amyloid accumulation in the heart, thus reducing the risk of developing AD-associated amyloid cardiomyopathy and cardiovascular disease.},
  language  = {en}
}
@article{WagnerSadekDybkovaetal.2021,
  author    = {Wagner, Michael and Sadek, Mirna S. and Dybkova, Nataliya and Mason, Fleur E. and Klehr, Johann and Firneburg, Rebecca and Cachorro, Eleder and Richter, Kurt and Klapproth, Erik and Kuenzel, Stephan R. and Lorenz, Kristina and Heijman, Jordi and Dobrev, Dobromir and El-Armouche, Ali and Sossalla, Samuel and K{\"a}mmerer, Susanne},
  title     = {Cellular mechanisms of the anti-arrhythmic effect of cardiac PDE2 overexpression},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22094816},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285888},
  year      = {2021},
  abstract  = {Background: Phosphodiesterases (PDE) critically regulate myocardial cAMP and cGMP levels. PDE2 is stimulated by cGMP to hydrolyze cAMP, mediating a negative crosstalk between both pathways. PDE2 upregulation in heart failure contributes to desensitization to β-adrenergic overstimulation. After isoprenaline (ISO) injections, PDE2 overexpressing mice (PDE2 OE) were protected against ventricular arrhythmia. Here, we investigate the mechanisms underlying the effects of PDE2 OE on susceptibility to arrhythmias. Methods: Cellular arrhythmia, ion currents, and Ca\(^{2+}\)-sparks were assessed in ventricular cardiomyocytes from PDE2 OE and WT littermates. Results: Under basal conditions, action potential (AP) morphology were similar in PDE2 OE and WT. ISO stimulation significantly increased the incidence of afterdepolarizations and spontaneous APs in WT, which was markedly reduced in PDE2 OE. The ISO-induced increase in I\(_{CaL}\) seen in WT was prevented in PDE2 OE. Moreover, the ISO-induced, Epac- and CaMKII-dependent increase in I\(_{NaL}\) and Ca\(^{2+}\)-spark frequency was blunted in PDE2 OE, while the effect of direct Epac activation was similar in both groups. Finally, PDE2 inhibition facilitated arrhythmic events in ex vivo perfused WT hearts after reperfusion injury. Conclusion: Higher PDE2 abundance protects against ISO-induced cardiac arrhythmia by preventing the Epac- and CaMKII-mediated increases of cellular triggers. Thus, activating myocardial PDE2 may represent a novel intracellular anti-arrhythmic therapeutic strategy in HF.},
  language  = {en}
}