NHLBI Working Group

The Interface between Thrombosis and Inflammation

Executive Summary

Complete Meeting Report

The National Heart, Lung, and Blood Institute convened a Working Group of researchers and physicians on July 30, 2007, to identify the research areas of inflammation-related thrombosis. Dr. Charles Peterson, Director of the Division of Blood Diseases and Resources, welcomed the participants and charged the Working Group to produce recommendations and to advise on the promising areas where NHLBI leadership would greatly benefit scientific advancement. The chairman, Dr. Douglas Cines, introduced the subject and led the discussion of Scientific Themes that emerged from the pre-meeting communication with the Working Group participants.

Outcome:

Thrombotic complications in vascular diseases are a leading cause of morbidity and mortality in the United States. Activation of inflammatory and coagulation pathways is important in the pathogenesis of vascular disease. There is a growing body of evidence that extensive cross-talk between these two systems exists. Inflammation leads to activation of coagulation; however coagulation also significantly affects inflammatory activity. A better understanding of how inflammatory and prothrombotic pathways are linked at the cellular and molecular levels may lead to novel therapeutic approaches targeting either or both pathological mechanisms.

Recommendations:

The following recommendations have been suggested by this Working Group (not prioritized):

1. Achieve better understanding of the interaction between leukocytes and platelets with each other and both cell types alone and together with the endothelium.
2. Investigate how the cellular component of hemostasis affects the immune system.
3. Study phenotypic reprogramming of circulating and vascular cells by inflammatory mediators.
4. Investigate the effect of bioactive molecules from platelets and leukocytes, and the vascular response.
5. Study activation of platelets/leukocytes by novel stimulants (bacteria, viruses, endo/exotoxins, DNA) that may act through unique pathways.
6. Define/identify the receptors, ligands and substrates that are induced by inflammation within the vessel wall as well as in the circulation and study the seqeuale of these changes on signal transduction.
7. Study coagulation proteins/receptors/pathways that have dual functions in coagulation and inflammation.
8. Further investigate the formation and modulation of the provisional matrix.
9. Develop a core facility for aging of animals.
10. Develop animal models of inflammation.
11. Implement the Biologic Systems approaches.
12. Develop novel techniques to visualize and monitor vascular pathology in vivo.
13. Further investigate the formation and modulation of the provisional matrix.

Publication Plans:

Working Group recommendations have been partially implemented into the initiative for the NHLBI Idea Forum on August 8, 2007.

Working Group Members (alphabetically):

• Douglas Cines, MD (Chair)
• Jane Freeman, MD
• Jose Lopez, MD
• Rodger McEver, MD
• Peter Newman, PhD
• Guy Reed, MD
• Wolfram Ruf, MD
• Dudley Strickland, PhD
• Denisa Wagner, PhD
• Andrew Weyrich, PhD
• Randall Worth, PhD

NHLBI Participants:

• Charles Peterson, MD
• Pankaj Ganguly, PhD
• Traci Mondoro, PhD
• Henry Chang, MD
• Rebecca Link, PhD
• Rita Sarkar, PhD
• Stephen Goldman, PhD
• Andrei Kindzelski, MD, PhD - NHLBI Contact: (301)402-0658
kindzelskial@nhlbi.nih.gov

• Craig Hooper, PhD - CDC Member

Last updated: October 4, 2007