Abstract 16633: Cardiac Myosin Binding Protein-C Prevents Immune Response-Triggered Cardiac Myocyte Death During Inflammation
Infections triggering decompensation in heart failure patients suggest involvement of an innate immune response. Cardiac myosin binding protein-C (MyBPC3) is a heart muscle thick filament protein that possesses immunoglobulin-like domains. Similar to MyBPC3, the cluster of differentiation 74 (CD74) has been shown to bind directly to myosin in lymphocytes and CD74 shares significant sequence homology to MyBPC3. Thus, we reasoned that MyBPC3, like CD74, may serve to influence immune recognition and susceptibility of damaged cardiac myocytes to apoptosis and immune-mediated cell death. We tested this hypothesis by comparing the cellular immune response and in vivo cardiac function after low dose lipopolysaccharide (LPS) treatment on wild-type (WT) vs. MyBPC3 null (MyBPC3(KO)) mice while using saline injections as control over a 7 day period. Flow-cytometric analyses showed that B and γδ-T lymphocytes from MyBPC3(KO) exhibit increased activation than WT mice (mean fluorescence intensity (MFI) of major histocompatibility complex (MHCII)). TUNEL staining demonstrated that LPS caused greater increases in apoptosis in MyBPC3(KO) hearts. Echocardiography revealed that LPS caused increases in left ventricular wall thickness and worsening of diastolic dysfunction only in MyBPC3(KO) hearts. The diastolic function was assessed by E/Ea ratio (E=mitral blood flow Doppler, Ea=tissue Doppler of myocardium) at early diastole. These data show that lack of MyBPC3 facilitated activation of an innate immune response that accelerated cardiac myocyte apoptosis, ultimately resulting in heart dysfunction. Thus, MyBPC3 appears to protective cardiac myocytes from innate, immune response-triggered death during inflammation.
- © 2013 by American Heart Association, Inc.