Publication
Antibodies aggravate the development of ischemic heart failure
| dc.contributor.author | Keppner, Lea | |
| dc.contributor.author | Heinrichs, Margarete | |
| dc.contributor.author | Rieckmann, Max | |
| dc.contributor.author | Jocelyne, Demengeot | |
| dc.contributor.author | Frantz, Stefan | |
| dc.contributor.author | Hofmann, Ulrich | |
| dc.contributor.author | Ramos, Gustavo | |
| dc.date.accessioned | 2020-03-30T09:58:54Z | |
| dc.date.available | 2020-04-01T00:30:09Z | |
| dc.date.issued | 2018-08 | |
| dc.description.abstract | Heart-specific antibodies have been widely associated with myocardial infarction (MI). However, it remains unclear whether autoantibodies mediate disease progression or are a byproduct of cardiac injury. To disambiguate the role of immunoglobulins in MI, we characterized the development of ischemic heart failure in agammaglobulinemic mice (AID-/-μS-/-). Although these animals can produce functional B cells, they cannot synthesize secretory IgM (μS-/-) or perform Ig class switching (AID-/-), leading to complete antibody deficiency. Agammaglobulinemia did not affect overall post-MI survival but resulted in a significant reduction in infarct size. Echocardiographic analyses showed that, compared with wild-type infarcted control mice, AID-/-μS-/- mice exhibited improved cardiac function and reduced remodeling on day 56 post-MI. These differences remained significant even after animals with matched infarct sizes were compared. Infarcted AID-/-μS-/- mice also showed reduced myocardial expression levels of transcripts known to promote adverse remodeling, such as matrix metalloproteinase-9, collagen type I a1, collagen type III a1, and IL-6. An unbiased screening of the heart reactivity potential in the plasma of wild-type MI animals revealed the presence of antibodies that target the myocardial scar and collagenase-sensitive epitopes. Moreover, we found that IgG accumulated within the scar tissues of infarcted mice and remained in close proximity with cells expressing Fcγ receptors (CD16/32), suggesting the existence of an in situ IgG-Fcγ receptor axis. Collectively, our study results confirm that antibodies contribute to ischemic heart failure progression and provide novel insights into the mechanisms underlying this phenomenon. NEW & NOTEWORTHY Our study sheds some light on the long-standing debate over the relevance of autoantibodies in heart failure and might stimulate future research in the field. The observation of extracellular matrix-specific antibodies and the detection of Fcγ receptor-expressing cells within the scar provide novel insights into the mechanisms by which antibodies may contribute to adverse remodeling. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.doi | 10.1152/ajpheart.00144.2018 | pt_PT |
| dc.identifier.issn | 0363-6135 | |
| dc.identifier.uri | http://hdl.handle.net/10400.7/948 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | American Physiological Society | pt_PT |
| dc.relation | Deutsche Forschungsgemein- schaft (DFG; SFB 688, TPA10) | pt_PT |
| dc.relation | Interdisciplinary Center for Clinical Research-Würzburg | pt_PT |
| dc.relation | Graduate School of Life Sciences- Würzburg | pt_PT |
| dc.subject | Agammaglobulinemia | pt_PT |
| dc.subject | Animals | pt_PT |
| dc.subject | Autoantibodies | pt_PT |
| dc.subject | Disease Models, Animal | pt_PT |
| dc.subject | Extracellular Matrix | pt_PT |
| dc.subject | Fibrosis | pt_PT |
| dc.subject | Heart Failure | pt_PT |
| dc.subject | Immunoglobulin M | pt_PT |
| dc.subject | Male | pt_PT |
| dc.subject | Mice, Inbred C57BL | pt_PT |
| dc.subject | Mice, Transgenic | pt_PT |
| dc.subject | Myocardial Infarction | pt_PT |
| dc.subject | Myocarditis | pt_PT |
| dc.subject | Myocardium | pt_PT |
| dc.subject | Receptors, IgG | pt_PT |
| dc.subject | Ventricular Function, Left | pt_PT |
| dc.subject | Ventricular Remodeling | pt_PT |
| dc.subject | Immunoglobulin Class Switching | pt_PT |
| dc.title | Antibodies aggravate the development of ischemic heart failure | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | H1367 | pt_PT |
| oaire.citation.issue | 5 | pt_PT |
| oaire.citation.startPage | H1358 | pt_PT |
| oaire.citation.title | American Journal of Physiology-Heart and Circulatory Physiology | pt_PT |
| oaire.citation.volume | 315 | pt_PT |
| person.familyName | Demengeot | |
| person.givenName | Jocelyne | |
| person.identifier | 21837 | |
| person.identifier.ciencia-id | 3A12-B260-A36C | |
| person.identifier.orcid | 0000-0002-4761-614X | |
| person.identifier.rid | K-8072-2014 | |
| person.identifier.scopus-author-id | 6603702602 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | eda6ec95-9595-42b6-9dfe-078e88d8cb2b | |
| relation.isAuthorOfPublication.latestForDiscovery | eda6ec95-9595-42b6-9dfe-078e88d8cb2b |