The Center for Cardiovascular Diagnostics and Prevention, chaired by Stanley Hazen, M.D., Ph.D., was founded in 2003. The Center is composed of eight faculty members, who have joint appointments in clinical and basic science departments, and has a total staff of 44.
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. 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 trial use through the Preventive Research Lab (PRL).
Stanley L. Hazen, M.D., Ph.D. – Chair, Center for Cardiovascular Diagnostics & Prevention
Staff, Department of Cell Biology
Section Head, Preventive Cardiology & Rehabilitation, Department of Cardiovascular Medicine
Dr. Hazen's current research programs are:
• Role of myeloperoxidase in cardiovascular disease
• HDL structure, function and dysfunction
• Oxidized phospholipids as pattern recognition ligands for macrophage CD36
• Peroxidases and the origins of tissue injury in asthma
• Molecular and genetic determinants of atherosclerotic plaque progression and vulnerability
Leslie Cho, M.D., F.A.C.C. -
Staff, 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:
• Exploring signaling integration of proinflammatory pathways by scavenger receptors
• Examining how the IKappa B kinase (IKK) is activated by various proinflammatory signals
• Developing inhibitors of specific protein:protein interactions
Ariel E. Feldstein, M.D.
Associate Staff, Department of Cell Biology
Staff, Department of Pediatric Gastroenterology
Dr. Feldstein’s current research programs are:
• Characterizing the lysosomal – mitochondrial crosstalk in in-vitro cell models and in-vivo murine models of steatohepatitis
• Characterizing mechanisms that initiate mitochondrial reactive oxygen production in models of nonalcoholic and alcoholic steatohepatitis
• Defining the mechanisms responsible for disease progression and fibrogenesis in steatohepatitis
• Characterizing links between lipid metabolism, tumor survival and chemotherapy resistance
Thomas McIntyre, Ph.D.
Staff, Department of Cell Biology
Staff, Department of Cardiovascular Medicine
Dr. McIntyre’s current research programs are:
• 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
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, IVUS 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
W.H. Wilson Tang, M.D., FACC, FAHA
Assistant Staff, Department of Cell Biology
Staff, Department of Cardiovascular Medicine
Dr. Tang’s current research programs are:
• Role of myeloperoxidase and oxidant stress in heart failure
• Novel biomarkers in heart failure disease progression
• Metabolic Modulation and arginine metabolic pathways in heart failure
• Genetic determinants of 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 II Core Facility functions as both an investigative and a service facility. The main focus of the core is to help the investigators to develop analytical methods for identification and quantification of biomarkers in biological materials such as plasma and urine. Connected to the PRL Core, the fully equipped core also provides novel biomarker analyses, markers of oxidant stress (e.g. F2-Isoprostanes) and proteomics-based studies are performed. The Mass Spectrometry II Core is equipped with triple quadrupole mass spectrometer and analytical HPLC systems.