Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2e. Improve prevention and treatment strategies for aortic aneurysms to prevent their progression, rupture, and dissection

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Overview

This goal will address both thoracic aortic aneurysms (TAAs) and abdominal aortic aneurisms (AAAs). Aortic aneurysms are life threatening conditions and represent the thirteenth leading cause of death in the U.S. The most common source of premature mortality associated with aortic aneurysms is acute dissections (more common to TAA) or rupture (more common to AAA). No strategy exists that can effectively identify which aortic aneurysm will dissect or rupture. Pharmacologic treatment strategies mainly treat risk factors such as hypertension. For both TAAs and AAAs, close monitoring of patients and elective surgery or endovascular repair to avoid rupture or dissection are the standard practice. Aortic aneurysms are more common in patients over age 60 years. However, those related to genetic conditions affect younger people. This is especially true for genetically induced TAAs (e.g., in Marfan, Loeys-Dietz, and Type IV Ehlers-Danlos syndromes). About 20 percent of TAAs and 15-25 percent of AAAs are known to be genetically induced. Only a small percentage of the responsible mutations have been identified, and the affected genes or genetic regions for the two types are different. TAAs and AAAs also have different pathologies and risk factors. This research seeks to facilitate a comprehensive approach for increasing our fundamental understanding of TAAs and AAAs, and to improve prevention, diagnosis, and treatment strategies.

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Investigate the genetic and environmental factors associated with the development and progression of TAA and AAA.
  • Investigate the fundamental biological and physiological mechanisms responsible for aneurysm formation and progression (for example, the role of TGF-ß signaling, matrix metalloproteinases, smooth muscle cell function, atherosclerosis, inflammation, and wall stress).
  • Based on mechanistic insight, identify targets for preventive therapy.
  • Understand the sex differences in the development and progression of aortic aneurysms in order to identify optimal therapies for all patients at risk.
  • Develop animal models of TAA and AAA that mimic the human disease.
  • Identify biomarkers (genetic, plasma, or structural) that predict the risk of rupture or dissection of aneurysms.

Translational Research:

  • Confirm pharmacotherapy targets in proof-of-concept studies.
  • Develop and refine minimally or noninvasive imaging technologies for early detection and assessment of aneurysms prone to rupture or dissection.
  • Develop improved endovascular stent grafts for prevention and repair of aortic dissection and rupture.
  • Establish phase I-II studies of preventive or therapeutic interventions.

Clinical Research:

  • Test biomarkers that are predictive of dissection and rupture in population studies.
  • Investigate the impact of pharmacologic interventions on clinical outcomes in patients with, or predisposed to, aortic aneurysms.
  • Evaluate the optimal approach and timing to surgical and percutaneous interventions to improve clinical outcomes in patients with aortic aneurysms.

Contributing Sources:

September 2008

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