Agammaglobulinemic mice lacking antibodies exhibited improved cardiac function and reduced adverse remodeling 56 days post-myocardial infarction compared with wild-type controls.
Does complete antibody deficiency improve cardiac function and reduce adverse remodeling post-myocardial infarction in mice?
Complete antibody deficiency in mice reduces infarct size, improves cardiac function, and attenuates adverse remodeling post-myocardial infarction, suggesting antibodies actively contribute to ischemic heart failure progression.
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.
Keppner et al. (Fri,) conducted a other in Ischemic heart failure post-myocardial infarction. Agammaglobulinemia (antibody deficiency) vs. Wild-type control mice was evaluated on Cardiac function and remodeling post-MI. Agammaglobulinemic mice lacking antibodies exhibited improved cardiac function and reduced adverse remodeling 56 days post-myocardial infarction compared with wild-type controls.