Showing 2 ideas for tag "arterial"

Goal 3: Advance Translational Research

Increasing Regenerative Medical Strategies in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a complex, progressive condition characterized by high blood pressure in the lungs and restriction of flow through the pulmonary arterial system. Current PAH therapies mainly act of the vasoconstrictive component of the disease; however there is a widely accepted view that another contributor to the disease is an abnormal overgrowth of cells that line the pulmonary arteries, which... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

In the past twenty years, 12 PAH targeted-therapies have been approved by the FDA. This increase in disease state awareness and in the treatment armamentarium have contributed to an increase in average survival from 2.8 years to an estimated 8-10 years. However, current treatments primarily address the vasoconstrictive component of the disease and do not address the now accepted theory of post-apoptotic overgrowth of hyperproliferative cells of the pulmonary vessels. A number of circulating stem and progenitor cells, derived from the bone marrow, have been identified that could have roles in repair of the pulmonary vascular system when interacting with the quickly, abnormally growing cells in the lung vessels. Work in this area has been named as a future research opportunity in the NHLBI-ORDR Strategic Plan for Lung Vascular Research (Erzurum S, et al. 2010).

Feasibility and challenges of addressing this CQ or CC

Basic and translational research support is needed—including high-throughput approaches such as phage display and large-scale proteomic analysis—to better understand the relationship between circulating bone marrow-derived cells, lung-resident stem and progenitor cells, and endothelial cells of the pulmonary arterial system.

Name of idea submitter and other team members who worked on this idea Pulmonary Hyeprtension Association, Michael Gray, Katie Kroner

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Goal 2: Reduce Human Disease

What are the fundamental molecular mechanisms involved in the vascular response to interventional or surgical injuries?

The pathobiology of restenosis is intimal hyperplasia, a specific form of wound healing. This response to physical injury is essential to prevent hemorrhage and thus has evolved to be highly sensitive, intense, resilient and redundant. It involves a complex interplay between blood elements, endothelial integrity, leukocytes, macrophages, fibroblasts and smooth muscle cells. Modifying this multipronged response has proven... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Impact: Huge. If we can control the vascular response to injury, the effectiveness of current surgery and technology would dramatically increase while complications and the need for reinterventions would decrease. In coronary artery bypass and lower extremity bypass surgery, restenosis after endovascular interventions is becoming a highly common common indication. Even a modest reduction in the response to injury would have a significant impact.

Feasibility and challenges of addressing this CQ or CC

We need a fresh approach to understanding the response to physical vascular injuries, using all the tools of genomics and bioinformatics to determine the molecular sequence of events. Studies in cell culture, organ culture, small animal models to verify each step in designing therapeutic strategies. Restenosis lends itself to therapeutic strategies that can be applied ex vivo, such as in pretreatment of vein grafts, drug delivery from prosthetic grafts or stents. Drug delivery, duration and timing in the context of flowing blood is an engineering challenge that must be verified in vivo. Materials must be biocompatible, at times durable, at other times reabsorb able. The scope of this challenge is vast as features of intimal hyperplasia vary with the injury. In vein grafts stenosis can occur anywhere along the conduit. In prosthetic grafts it occurs only at the anastomosis. This problem requires highly collaborative multi disciplinary teams with creative communication structures. New forms of collaboration with industry should be entertained. In terms of policy we might consider how much should be spent on research after market to verify effectiveness and should those funds come from industry.

Name of idea submitter and other team members who worked on this idea Frank LoGerfo, M.D.

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