Antibodies aggravate the development of ischemic heart failure.

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...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research