Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2h. Advance understanding of the fundamental mechanisms regulating the function of the lymphatic vasculature in relation to cardiovascular diseases

Table of Contents

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

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Return to Goals of the Division of Cardiovascular Diseases Strategic Plan

Overview

The lymphatic vasculature is essential for the return of protein-rich extracellular fluid into the blood circulation, cellular transport of lymphocytes and the immune response, uptake of lipids from the gut, and the chronic inflammatory response. All organs, including the heart, have an extensive lymphatic system. Conceivably, this intimate association of the lymphatic vasculature and CV tissue suggests that a causal link may exist between lymphatic dysfunction and the pathogenesis of CV disease. For example, developmental abnormalities of the lymphatic system appear to be associated with cardiac malformations in children. In the adult, disruption or obstruction of the lymphatic system during surgery or perturbations in myocardial fluid homeostasis following a MI causes myocardial edema, triggering an inflammatory response, followed by tissue fibrosis. This sequence of events may contribute, in part, to heart failure or cardiac transplant rejection. Despite such a central role, development of the lymphatic system in concert with its role in maintaining the physiological integrity of CV tissue during development and in the adult is poorly understood. This goal highlights research to better understand the regulation of lymphatic function under physiological and pathological conditions in CV tissue and how changes in lymphatic function are relevant in the pathogenesis of CV disease. This knowledge will provide new insights and approaches for treating congenital heart disease, complications following congenital heart surgery, heart failure, vascular inflammatory diseases, including atherosclerosis and the chronic inflammatory state that contributes to transplant rejection.

Strategies to Accomplish this Goal May Entail:

Basic Research:

• Investigate the development of the lymphatic system and its role in congenital heart disease.
• Investigate the genetic and environmental factors causing lymphatic malfunctions, contributing to CV disease.
• Develop suitable animal models of lymphatic-related CV disorders to study underlying mechanisms and to evaluate therapeutic interventions.
• Develop high resolution and real-time molecular and diagnostic lymphatic imaging.
• Investigate the role of the lymphatic system in conditions such as inflammation and obesity, which contribute to CV disease.

Translational Research:

• Identify target molecules for treating lymphatic disorders that contribute to CV disease.
• Identify suitable panels of lymphatic-origin biomarkers for disorders that contribute to CV disease.
• Create patient registries and a lymphatic disease tissue bank to facilitate research in lymphatic disorders.

Clinical Research:

• Support a natural history study to understand the course of congenital lymphatic disorders linked to CV malformations.
• Conduct treatment trials with agents identified from basic and translational research.

Contributing Sources:

• NHLBI Strategic Plan Goals 1 and 2
• Recommendations from the NHLBI Strategic Plan Level One Final Reports:
  • Vascular Disease and Hypertension
  • Emerging and Evolving Technologies
  • From Discovery to Clinical Application
• NHLBI Workshops and Working Groups:
  • TARP Workshop: Inflammation and Perivascular Environment, November 2007
  • Trans-NIH Working Group on Lymphatic Research, September 2007
  • Trans-Institute Angiogenesis Research Program (TARP) Workshop, May 2004

September 2008