Metabolomic Analysis of Atherothrombosis

Acute myocardial infarction (MI) remains a leading cause of death worldwide. It is most commonly caused by thrombi overlying disrupted atherosclerotic plaques.

However, while plaque disruption often precipitates thrombosis, autopsy studies have shown that plaque rupture alone is not sufficient to cause an occlusive coronary thrombus resulting in acute MI. As many as 79% of plaque ruptures do not result in occlusive coronary thrombosis.

Determining the factor(s) that "drive" a pathological, as opposed to a homeostatic or subclinical, response to plaque disruption is the essence of my work. My laboratory has created a unique cohort of thrombotic and non-thrombotic MI from which we identified metabolites that are significantly different at the time of acute thrombotic MI relative to the quiescent stable state within subjects and distinct from any change observed in non-thrombotic MI and stable coronary artery disease (CAD) patients over the same time course.

We now propose conducting a targeted quantification of these metabolites in an extended cohort, evaluating the mechanistic effect of candidate metabolites on platelet activation, as well as mechanisms of plaque disruption and further evaluating diagnostic specificity by developing a metabolomics based test for thrombotic MI. Defining the "drivers" of thrombotic MI will be of diagnostic, prognostic, therapeutic and preventative value.

Related Publications

Principal Investigator

Andrew DeFilippis

Andrew DeFilippis, M.D.

Assistant Professor of Medicine
Director, Cardiovascular Disease Prevention
Adjunct Assistant Professor of Medicine,
Johns Hopkins University
E-mail Andrew DeFilippis


  • M.D.: Georgetown University School of Medicine, Washington, D.C.

  • Residency: Internal Medicine, Emory University School of Medicine, Atlanta, GA; Cardiovascular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD

  • Fellowship: Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD

  • M.Sci.: Clinical Research (Clinical Research Curriculum Award (NIH K30), Emory University School of Medicine, Atlanta, GA

Research Focus

  • Biomarker development for acute myocardial infarction (atherothrombotic and non-atherothrmbotic)

  • Cardiovascular risk prediction

  • Plaque disruption and coronary thrombosis

  • Omics