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Antibodies aggravate the development of ischemic heart failure.

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Antibodies aggravate the development of ischemic heart failure.

Am J Physiol Heart Circ Physiol. 2018 Aug 10;:

Authors: Keppner L, Heinrichs M, Rieckmann M, Demengeot J, Frantz S, Hofmann U, Ramos G

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 (HF) in agammaglobulinemic mice (AID-/-μS-/-). While these animals can produce functional B-cells, they cannot synthesize secretory IgM (μS-/-) or perform immunoglobulin 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 to the WT infarcted controls, the AID-/-μS-/- mice exhibited improved cardiac function and reduced remodeling at 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 Mmp9, Col1a1, Col3a1, and Il6. An unbiased screening of the heart-reactivity potential in the plasma of WT 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, FcγR), suggesting the existence of an in situ IgG-Fcγ receptor axis. Collectively, our study results confirm that antibodies contribute to ischemic HF progression and provide novel insights into the mechanisms underlying this phenomenon.

PMID: 30095974 [PubMed – as supplied by publisher]

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