Precursor proadrenomedullin influences cardiomyocyte survival and local inflammation related to myocardial infarction

Proceedings of the National Academy of Sciences of the United States of America
Svenja HinrichsDiana Lindner

Abstract

Increased adrenomedullin (ADM) levels are associated with various cardiac diseases such as myocardial infarction (MI). ADM is cleaved off from the full-length precursor protein proadrenomedullin (ProADM) during its posttranslational processing. To date, no biological effect of ProADM is reported, while ADM infusion leads to antiapoptotic effects and improved cardiac function. Using an MI mouse model, we found an induction of ProADM gene as well as protein expression during the early phase of MI. This was accompanied by apoptosis and increasing inflammation, which substantially influence the post-MI remodeling processes. Simulating ischemia in vitro, we demonstrate that ProADM expression was increased in cardiomyocytes and cardiac fibroblasts. Subsequently, we treated ischemic cardiomyocytes with either ProADM or ADM and found that both proteins increased survival. This effect was diminishable by blocking the ADM1 receptor. To investigate whether ProADM and ADM play a role in the regulation of cardiac inflammation, we analyzed chemokine expression after treatment of cells with both proteins. While ProADM induced an expression of proinflammatory cytokines, thus promoting inflammation, ADM reduced chemokine expression. On leukocyt...Continue Reading

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Citations

Mar 20, 2019·Basic Research in Cardiology·Lucas BacmeisterDiana Lindner
May 24, 2019·Science Translational Medicine·Katharina ScherschelChristian Meyer
Feb 23, 2020·Journal of Clinical Medicine·Raúl MéndezRosario Menéndez
Jul 31, 2020·JAMA Cardiology·Diana LindnerDirk Westermann
Feb 10, 2021·Clinical Pharmacology and Therapeutics·Linda B S AulinJ G Coen van Hasselt
Aug 10, 2021·Frontiers in Pharmacology·Wenkai YangJianguo Wu
Aug 16, 2021·European Heart Journal·Julian U G Wagner, Stefanie Dimmeler

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