Endothelial Progenitor Cells

Endothelial injury is an early event in the pathogenesis of atherosclerosis and its sequelae. Experimental studies suggest that circulating endothelial progenitor cells (EPC) contribute to the maintenance of endothelial integrity via incorporation into sites of endothelial injury or release of autocrine/paracrine factors. Prior human research suggests that EPC number and function are reduced in individuals with multiple coronary risk factors or established coronary artery disease. It is unknown whether common genetic variation accounts for some of the inter-individual variability in circulating EPCs. Genetic variants that influence concentrations of these molecules could potentially alter susceptibility to endothelial dysfunction and coronary artery disease.

EPC number and proliferative function were assessed on specimens obtained from Framingham Offspring Study participants attending the 8th quadrennial examination. EPC number was assessed using flow cytometry to define the following cell populations: CD34+, AC133+, CD34+/KDR+, CD31+/CD45+. Proliferative function was assayed with a standard EPC colony forming unit assay.

In 1948, researchers recruited men and women from the town of Framingham, Massachusetts, beginning the first round of extensive physical examinations and lifestyle interviews that would later be analyzed for common patterns related to CVD development.

Initially, the Framingham Heart Study enrolled 5,209 men and women from the Framingham area who were between the ages of 28 and 62 years. Beginning in 1971, the Framingham Heart Study enrolled 5,124 men and women, who were either offspring of the original cohort or spouses of those offspring. In 2002, 4,095 third generation participants (men and women) were enrolled.

During each clinic exam cycle, the participants undergo a detailed examination including physical examination, medical history, laboratory testing, and electrocardiogram. Over the years, other tests (that may not be performed at every exam cycle) have included pulmonary function, lifestyle, physical function, cognitive function questionnaires, and various noninvasive cardiovascular tests including echocardiograms. The content of each exam cycle differs for Original, Offspring and Generation 3 cohorts and can be found in the Exam Cycle Protocol Manuals.

• Study Weblinks:
  • The Framingham Heart Study
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
• Total number of consented subjects: 2134
• Subject Sample Telemetry Report (SSTR)

Offspring cohort, 8th examination

The Generation 1 (or Original) cohort Exam 1 took place between 1948 and 1953. Biennial exams have continued to the present. Exam 29 took place between 2006 and 2007. Exam 30 began in 2008.

The Generation 2 (or Offspring) cohort Exam 1 took place between 1971 and 1975. This cohort on average has been examined every three to four years. However, there was an eight year gap between Exam 1 and Exam 2 and a seven year gap between Exam 7 and Exam 8. Exam 8 took place between 2005 and 2008.

The Generation 3 cohort Exam 1 took place between 2002 and 2005. Exam 2 began in 2008.

The New Offspring Spouse cohort Exam 1 took place between 2003 and 2005. Exam 2 began in 2008.

• Primary Phenotype: Cardiovascular System
• Coronary Artery Disease

• Principal Investigator
  • Thomas Wang, MD. Massachusetts General Hospital, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
• Co-Investigators
  • Kenneth S. Cohen, MD, PhD. University of Chicago, Chicago, IL, USA.
  • Stanley Shaw, MD, PhD. Massachusetts General Hospital, Boston, MA, USA and Broad Institute, Cambridge, MA, USA.
  • Vasan S. Ramachandran, MD. Boston University, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Martin G. Larson, ScD. Boston University, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
  • Emelia J. Benjamin, MD, ScM. Boston University, Boston, MA, USA and Framingham Heart Study, Framingham, MA, USA.
• Funding Source
  • NO1-HC-25195. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • R01-HL-083197. National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.