Matrix Signaling Subsequent to a Myocardial Infarction: A Proteomic Profile of Tissue Factor Microparticles

JACC Basic Transl Sci. 2017 Oct 30;2(5):529-542. doi: 10.1016/j.jacbts.2017.04.004. eCollection 2017 Oct.

Abstract

This study investigated the release and proteomic profile of tissue factor microparticles (TFMPs) prospectively (up to 6 months) following a myocardial infarction (MI) in a chronic porcine model to establish their utility in tracking cellular level activities that predict physiologic outcomes. Our animal groups (n = 6 to 8 each) consisted of control, noninfarcted (negative control); infarcted only (positive control); and infarcted animals treated with cardiac resynchronization therapy (CRT) and a β-blocker (BB) (metoprolol succinate). The authors found different protein profiles in TFMPs between the control, infarcted only group, and the CRT + BB treated group with predictive impact on the outward phenotype of pathological remodeling after an MI within and between groups. This novel approach of monitoring cellular level activities by profiling the content of TFMPs has the potential of addressing a shortfall of the current crop of cardiac biomarkers, which is the inability to capture composite molecular changes associated with chronic maladaptive signaling in a spatial and temporal manner.

Keywords: ADRB1, β1-adrenergic receptor; ADRB2, β2-adrenergic receptor; AR, adrenergic receptor; ARRB1, β1-arrestin; BB, β-blocker; CRT, cardiac resynchronization therapy; EDV, end-diastolic volume; EF, ejection fraction; ELISA, enzyme-linked immunosorbent assay; ESV, end-systolic volume; FACS, fluorescence-activated cell sorting; GRK, G-protein receptor kinase; HSP, heat shock protein; HUVEC, human umbilical vein endothelial cell; LVAd MV, left ventricular area around the mitral valve at diastole; LVAd PM, left ventricular area around the papillary muscle at diastole; LVAs MV, left ventricular area around the mitral valve at systole; LVAs PM, left ventricular area around the papillary muscle at systole; MI, myocardial infarction; MP, microparticle; PCR, polymerase chain reaction; TF, tissue factor; TFMP, tissue factor–bearing microparticle; TnT, troponin T; Yucatan mini swine; cAMP, cyclic adenosine monophosphate; chronic ischemic cardiomyopathy; matrix signaling; myocardial infarction; tissue factor-bearing microparticles; βAR signaling.