Center for Cardiovascular Diagnostics & Prevention

The Center for Cardiovascular Diagnostics and Prevention, chaired by Stanley Hazen, M.D., Ph.D., was founded in 2003. The Center employs faculty members who have joint appointments in clinical and basic science departments, and has a total staff of 49.

The Center provides diverse Core Services that are available to internal and external laboratories. Core Services:

The Center hosts a diverse range of research programs whose central theme is an emphasis on extending basic research observations into clinical studies in the general areas of inflammation and preventive cardiovascular medicine. Some studies are aimed at defining novel inflammatory mediators of cardiovascular disease and their potential utility as diagnostic and prognostic indicators of risk, responses to therapies, or novel targets for therapeutic interventions. A further area of study is in understanding the role of intestinal micro flora in cardiometabolic diseases. Additional studies focus on the atheroprotective lipoprotein HDL and HDL-associated protein structure, function, and mechanisms for rendering HDL "dysfunctional".

Another major research effort focuses on genetic and molecular determinants of atherosclerotic plaque progression and vulnerability, including the role of structurally distinct oxidized phospholipids as inflammatory mediators of diverse disease processes. Research on platelet activating factor (PAF), PAF-like oxidized phospholipids, and catabolic pathways responsible for clearance of these lipidic inflammatory mediators, is ongoing. Complementary studies also focus on platelet function, mechanisms of hyperreactivity, and involvement in atherothrombotic disease. The role of oxidant stress, nitric oxide and alterations in arginine metabolism are being studied in the setting of myocardial dysfunction and atherosclerotic progression. Yet additional research studies focus on genetic determinants of cholesterol and fat absorption, dyslipidemia and the participation of lipid accumulation and apoptosis in hepatic pathophysiology. Finally, research efforts are also focused on defining the clinical utility of molecular markers of distinct oxidation pathways as quantitative indices of asthma presence, severity and response to therapy.

The Center is home to several core facilities designed to support human clinical trials laboratory research, including an accredited clinical reference laboratory and a mass spectrometry analytical laboratory. One of the Center’s goals is to develop and validate novel diagnostic tests for cardiovascular and other inflammatory diseases. These tests are then made available for clinical trials use through the Preventive Research Lab (PRL).

Research Programs

Stanley L. Hazen, M.D., Ph.D.
Chair, Center for Cardiovascular Diagnostics & Prevention
Vice Chair, Translational Research, Lerner Research Institute
Staff, Department of Cell Biology
Section Head, Preventive Cardiology & Rehabilitation, Department of Cardiovascular Medicine

Dr. Hazen's current research programs are:

  • Role of gut flora in cardiometabolic diseases
  • Role of myeloperoxidase in cardiovascular disease
  • HDL structure, function and dysfunction
  • Peroxidases and the origins of tissue injury in asthma
  • Molecular and genetic determinants of atherosclerotic plaque progression and vulnerability

Wu, Z et al, J. Biol. Chem. (2011)286:12495
Wu, Z et al, J. Biol. Chem. (2011)286:12495
Wang, Z et al, Nature (2011) 472(7341):57
Wang, Z et al, Nature (2011) 472(7341):57

Leslie Cho, M.D., F.A.C.C.
Staff, Department of Cardiovascular Medicine
Section Head, Preventive Cardiology & Rehabilitation, Department of Cardiovascular Medicine Medical Director, Preventive Cardiology Clinic
Director, Women's Center for Cardiovascular Medicine

Dr. Cho ’s current research programs are:

  • Novel biomarkers in coronary artery disease and peripheral artery disease
  • Gender differences in atherosclerosis
  • CoQ10 and statin intolerance
  • High fiber diet and inflammation
  • Women and Cardiovascular disease

Joseph DiDonato, Ph.D.
Laboratory Director, Center for Cardiovascular Diagnostics & Prevention
Staff Scientist, Department of Cell Biology
Assistant Staff, Department of Cardiovascular Medicine

Dr. DiDonato’s current research programs are:

  • Defining novel pathways of platelet activation
  • Identifying controlling new platelet pathways necessary to thrombosis
  • Establishing platelet RNA processing as a novel inflammatory marker

Thomas McIntyre, Ph.D.
Staff, Department of Cell Biology
Staff, Department of Cardiovascular Medicine

Dr. McIntyre’s current research programs include:

  • Defining the role of mitochondria in human disease
  • Exploring the in vivo metabolism of biologically active phospholipids
  • Defining novel pathways of platelet activation
  • Establishing platelet RNA processing as a novel inflammatory marker

Platelets immobilized in occlusive carotid artery thrombi express the inflammatory cytokine IL-1β. Fluorescent confocal microscopy shows IL-1β (green) is produced within a thrombus 1 hour after damaging the carotid artery. IL-1β staining shows the cytokine is associated with platelet membranes (red) and not nucleated (blue) mononuclear cells that have infiltrated the clot. This shows IL-1β, a master cytokine that activates endothelium and leukocytes, is rapidly produced by RNA splicing and translation in platelets.

Stephen J. Nicholls, M.D., Ph.D., F.A.C.C.
Clinical Director, Center for Cardiovascular Diagnostics & Prevention
Assistant Staff, Department of Cell Biology
Associate Staff, Department of Cardiovascular Medicine
Director, Atherosclerosis Imaging Core Lab

Dr. Nicholls’s current research programs are:

  • Defining the influence of plasma lipoproteins on molecular events in atherosclerosis
  • Defining novel pathways of inflammation and genetic determinants of plaque progression
  • Developing imaging modalities to study the natural history of atherosclerosis
  • Evaluating the impact of medical therapies on atherosclerosis

Ephraim Sehayek, M.D.
Assistant Staff, Department of Genomic Medicine Institute
Assistant Staff, Department of Cardiovascular Medicine

Dr. Sehayek’s current research programs are:

  • Discovery of human and mouse genes that modify sterol and fat absorption from the intestine
  • Discovery of human and mouse genes that modify bile acid metabolism
  • Defining the relationship of sterol and fat absorption to reverse cholesterol transport and atherosclerosis cardiovascular diseases

Ephraim Sehayek's Figure

W.H. Wilson Tang, M.D., FACC, FAHA
Staff, Department of Cell Biology
Staff, Department of Cardiovascular Medicine

Dr. Tang’s current research programs are:

  • Role of nitrative/oxidant stress and counter-regulatory pathways in heart failure and cardio-renal syndrome.
  • Novel biomarkers in heart failure disease progression .
  • Metabolic Modulation and arginine metabolic pathways in heart failure
  • Integrative genetics and metabolomic determinants of human cardiomyopathy

The Preventive Research Lab
Director - Frederick van Lente, Ph.D.
Manager
- Alan Pratt
Assistant Manager
- Sarah Neale

The Preventive Research Laboratory (PRL), housed within the Center for Cardiovascular Diagnostics & Prevention, functions as a full-service core reference laboratory for clinical and diagnostic laboratory studies. PRL is College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Act (CLIA) licensed, and serves as core facilities to the Cleveland Clinic Heart Center and the NIH-funded General Clinical Research Center. Many of the assays performed at PRL are CDC standardized. In addition to performing more 100 routine clinical diagnostic tests, PRL performs cutting-edge biochemical and genetic tests for the prediction, diagnosis and treatment of cardiovascular disease. Many novel diagnostic tests for cardiovascular disease developed within the Center are validated within PRL prior to implementation as high through-put assays. PRL also provides infrastructure with quality control oversight, and electronic storage/sample tracking procedures to effectively process blood, serum/plasma and DNA samples in support of clinical trials.

Mass Spectrometry II Core
Manager – Renliang Zhang, M.D., Ph.D.

The Mass Spectrometry Core functions as both an investigative and a service facility. The main focus of the core is to help investigators to develop analytical methods using liquid chromatography tandem mass spectrometry for identification and quantification of biomarkers in biological materials such as plasma and urine. Connected to the PRL Core, the fully equipped core provides novel biomarker analysis, markers of oxidant stress (e.g. F2-Isoprostanes) and proteomics-based studies. The Mass Spectrometry Core is equipped with triple quadrupole mass spectrometer and analytical HPLC systems.