Heart failure and target organ damage
Cardiovascular disease (CVD) represents the most significant global health concern. Despite notable advancements in diagnosis and prevention, CVD persists as a leading cause of disability and mortality worldwide.??
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Heart failure is one of the heart diseases with the highest morbidity in Germany and worldwide. Every year, over 300,000 people suffer a heart attack in Germany alone. However, as the survival rate after myocardial infarction or heart failure has improved enormously in recent decades, various comorbidities have become much more common.?
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Currently, there are no curative treatments for preventing or slowing the progression of heart failure associated target organ damage.?
Heart failure-associated brain dysfunction?
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Over the past decade, medical advancements have significantly improved the survival rates for heart attacks. Yet, this extension in longevity might come at a cost as HF induces a chronic reduction in cerebral perfusion that negatively impacts patient prognosis and clinical outcome. Such chronic brain perfusion deficits are frequently accompanied by cognitive decline, which seriously impacts the patients’ quality of life, their ability to cope with their primary disease (e.g.,?through reduced treatment compliance), and have substantial social effects on families, friends, and society at large. Statistically, cognitive impairment is 5 times more prevalent in HF patients relative to the age-matched general population. To date, no curative treatments or strategies for preventing or slowing of cognitive decline associated with HF exist, which is mainly due to the lack of knowledge regarding the mechanisms underlying HF-mediated brain complications. Thus, new approaches to addressing this are urgently needed.?
Related Publications
Vanherle Lotte, Matthes Frank, Uhl Franziska E., Meissner Anja.
Ivacaftor therapy post myocardial infarction augments systemic inflammation and evokes contrasting effects with respect to tissue inflammation in brain and lung.
https://doi.org/10.1016/j.biopha.2023.114628
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Vanherle Lotte, Lidington Darcy, Vassallo Stefania, Skoug Cecilia, Bolz Steffen-Sebastian, Meissner Anja.
Restoring heart failure-induced long-term memory impairment by targeting the cystic fibrosis transmembrane regulator [Abstract].
https://doi.org/10.1111/jnc.15675
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Lidington Darcy, Fares Jessica C., Uhl Franziska E., Dinh Danny D., Kroetsch Jeffrey T., Sauvé Meghan, Malik Firhan A., Matthes Frank, Vanherle Lotte, Adel Arman, Momen Abdul, Zhang Hangjun, Aschar-Sobbi Roozbeh, Foltz Warren D., Wan Hoyee, Sumiyoshi Manabu, Macdonald R. Loch, Husain Mansoor, Backx Peter H., Heximer Scott P., Meissner Anja, Bolz Steffen-Sebastian.
CFTR therapeutics normalize cerebral?perfusion deficits in mouse?models of heart?failure and subarachnoid hemorrhage.
https://doi.org/10.1016/j.jacbts.2019.07.004
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Yang Jingli, Hossein Noyan-Ashraf M., Meissner Anja, Voigtlaender-Bolz Julia, Kroetsch Jeffrey T., Foltz Warren, Jaffray David, Kapoor Amita, Momen Abdul, Heximer Scott P., Zhang Hangjun, van Eede Matthijs, Henkelman R. Mark, Matthews Stephen G., Lidington Darcy, Husain Mansoor, Bolz Steffen-Sebastian.
Proximal cerebral arteries develop myogenic responsiveness in heart failure via tumor necrosis factor-α–dependent activation of Sphingosine-1-Phosphate signaling.
https://doi.org/10.1161/circulationaha.111.039644
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Kroetsch Jeffrey Thomas, Meissner Anja, Momen Abdul, Husain Mansoor, Bolz Steffen‐Sebastian.
TNFα is central to the augmented myogenic response of skeletal muscle resistance arteries in heart failure.
https://doi.org/10.1096/fasebj.25.1_supplement.1026.12
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Heart failure-mediated pulmonary distress?
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Cardiovascular and chronic lung diseases are an enormous health burden worldwide accounting for 4 of the top 6 causes of death according to the World Health Organization. Existing therapies can only slow down disease progression and therefore, new solutions are urgently needed. Traditionally, both are regarded separate entities but increasing evidence shows that the existing link between chronic cardiovascular and chronic lung diseases is largely underestimated and thus, integrated approaches toward deciphering this link on a molecular level are urgently needed.?
Related Funding
Swedish Foundation for International cooperation - STINT : Switching the gatekeeper in S1P homeostasis: the role of CFTR in chronic heart and lung diseases – funding period ?2020 – 2024
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Crafoordska Stiftelse:?The in heart failure – CFTR as critical modulator for cardiopulmonary distress – funding period 2019 – 2021
Related Publications
Vanherle Lotte, Matthes Frank, Uhl Franziska E., Meissner Anja.
Ivacaftor therapy post myocardial infarction augments systemic inflammation and evokes contrasting effects with respect to tissue inflammation in brain and lung.
https://doi.org/10.1016/j.biopha.2023.114628
PDF | BibTeX | RIS | DOI |
Uhl Franziska E., Vanherle Lotte, Meissner Anja.
Cystic fibrosis transmembrane regulator correction attenuates heart failure-induced lung inflammation.
https://doi.org/10.3389/fimmu.2022.928300
PDF | BibTeX | RIS | DOI |
Uhl Franziska E., Vanherle Lotte, Matthes Frank, Meissner Anja.
Therapeutic CFTR correction normalizes systemic and lung-specific S1P level alterations associated with heart failure.
https://doi.org/10.3390/ijms23020866
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