Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2c. Prevent initiation and progression of atherosclerosis/atherothrombosis

Table of Contents

• Overview
• Strategies to Accomplish This Goal May Entail
  • Basic Research
  • Translational Research
  • Clinical Research
• Contributing Sources

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Overview

The most effective approach to removing the burden of atherothrombotic disease is to prevent the initiation and progression of atherosclerosis. Substantial progress is likely to result from a more complete understanding of known and emerging risk factors. Additionally, evolving knowledge of biological pathways and their interactions that lead to atherothrombosis is likely to enhance our understanding of how and when best to intervene. Overall, this goal seeks improved understanding of the mechanisms underlying the initiation and progression of atherosclerosis as a basis for improved strategies for predicting and preventing atherothrombotic disorders and their sequelae.

Strategies to Accomplish this Goal May Entail:

Basic Research:

• Characterize inherited and environmental predispositions to atherosclerosis progression and to thrombosis across the life span.
• Expand understanding of biological pathways to elucidate new molecular targets to prevent the initiation and progression of atherosclerosis.
• Improve phenotyping; for example, develop improved imaging techniques for atherosclerosis, and phenotyping of endothelial cells, and stem cells, which may be linked to the atherosclerotic process.
• Define phenotypes of atherothrombosis through functional and expression studies. Identify and localize new genes and blood proteins and their modifications that account for phenotypic variance of the atherothrombotic state.
• Study the links between atherothrombosis, inflammation, immunity, and neurohormonal milieu. Develop cell-penetrating suppressors of inflammation for targeted delivery to vascular endothelium in atherothrombosis. Identify targets for developing a new class of inhibitors of cytokine signaling.
• Determine the proteomic and genomic signatures of an individual’s risk for developing atherothrombosis and its complications in vital organs.

Translational Research:

• Examine the impact of a new treatment on the intended biological target. An example is the change in serum HDL by a drug designed to induce regression of atherosclerosis by increasing HDL.
• Determine the effect of new interventions on atherosclerotic burden and acute coronary events.
• Develop new national standardization programs for CV biomarkers, to enhance utility in research and patient management (in collaboration with the Centers for Disease Control and Prevention.
• Develop and validate relevant animal models that predict or recapitulate human atherothrombotic disorders and that can be used to test new therapies.
• Develop biomarkers for prediction, early detection, and prognostication of atherothrombotic disorders.
• Develop imaging techniques to identify rupture-prone plaques.

Clinical Research:

• Develop phase III clinical trials of risk factor reduction for primary or secondary prevention of atherothrombotic clinical events.
• Implement studies utilizing the databases of clinical trials and epidemiologic studies to assess the effect of interventions on subpopulations, such as diabetics.
• Explore the interaction of genetics and diet to minimize atherosclerotic risk factors and disease risk.

Contributing Sources:

• NHLBI Strategic Plan Goals 1, 2 and 3
• Recommendations from the NHLBI Strategic Plan Level One Final Reports:
  • Coronary Artery Disease and Atherothrombosis
  • Regenerative and Reparative Medicine
  • Emerging and Evolving Technologies
  • From Discovery to Clinical Application
  • Personalized Medicine Planning
  • Bioinformatics and Computational Biology
  • Critical Role of Inflammation in Ischemic Disorders
  • Diagnosis and Treatment of Thrombotic Disorders
  • Translation, Implementation, and Community Research
• NHLBI Workshops and Working Groups:
  • NHLBI, Canadian Stroke Network, and NINDS 2005 Immunomodulation Strategies for Preventing Vascular Disease of the Brain and Heart, Damani, S.B. and Topol E.J.: Future Use of Genomics in Coronary Artery Disease. J. Am. Coll.Cardiol., 2007 50: 1933-1940.

September 2008