Goal 2: Reduce Human Disease

Role of vascular development in pulmonary hypertension

Does interrupted or aberrant pulmonary vascular development contribute to pulmonary hypertension?

Submitted by (@nhlbiforumadministrator)

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

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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16 net votes
28 up votes
12 down votes
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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

Submitted by (@societyforvascularsurgery)

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

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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2 net votes
3 up votes
1 down votes
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Goal 1: Promote Human Health

Screening for asymptomatic vascular disease

Does screening for asymptomatic vascular disease increase awareness, promote compliance with lifestyle interventions, and improve overall health?

Submitted by (@societyforvascularsurgery)

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

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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0 net votes
2 up votes
2 down votes
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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does anticoagulation with warfarin improve outcomes (time to clinical worsening, qualtiy of life, exercise capacity) in patients with pulmonary arterial hypertension treated with current oral/inhaled therapies? There are substantial "unknowns" and practice variation in anticoagulation in PAH. Resource utilization is also a factor here. We may either be helping patients (or hurting them with side effects) by using anticoagulation. ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

This is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

Name of idea submitter and other team members who worked on this idea : ATS Member

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2 net votes
2 up votes
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Goal 2: Reduce Human Disease

Vascular biology and the pathophysiology of sepsis

Unravel the cellular & molecular mechanisms related to the vascular biology of sepsis and related cardiovascular collapse. The goal is to develop a new scientific framework for the prevention of sepsis related morbidity and mortality by applying novel approaches to discover new targets for biomarkers and therapy by promoting multidisciplinary research required for scientific cross-talk between complementary research disciplines ...more »

Submitted by (@greg.martin)

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

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

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4 net votes
8 up votes
4 down votes
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Goal 4: Develop Workforce and Resources

Establishment of an independent study section on Pulmonary Vascular Biology and Translational Research

The research on pulmonary vascular biology including smooth muscle cell biology and endothelial cell biology and related pulmonary vascular diseases such as pulmonary hypertension and related right heart failure, and endothelial dysfunction in lung vascular inflammation and acute lung injury, as well as pulmonary embolism and lung transplantation has been rapidly expanding. The field is attracting an ever increasing ...more »

Submitted by (@yyzhao)

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

Details on the impact of addressing this CQ or CC :

Establishment of a study section on Pulmonary Vascular Biology and Translational Research will provide adequate funding to stimulate innovative research on this rapidly expanding field and promote translational research and thereby promote human health by providing potential novel therapeutic strategies for the devastating diseases such as pulmonary hypertension and acute lung injury.

Name of idea submitter and other team members who worked on this idea : Youyang Zhao, Kurt Denmark, Asrar B. Malik, Mark Gladwin, Jahar Bhattacharya, Michael Matthay, Sharon Rounds, Jason Yuan

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23 net votes
50 up votes
27 down votes
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Goal 1: Promote Human Health

Endoglin Regulates biolgy and signal transduction in vascular smooth muscle cells

Why loss of endoglin causes HHT is not known. Endoglin is expressed by vascular smooth muscle cells and endothelial cells.

What is the role of endogin on vascular smooth muscle cells and why its loss contributes to HHT and other vascular malformations

Submitted by (@mariannes.clancy)

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

Details on the impact of addressing this CQ or CC :

Vascular smooth muscle cells wrap around arteries and control their diameter.

Name of idea submitter and other team members who worked on this idea : Marianne Clancy MPA, Chris Hughes PhD

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1 net vote
1 up votes
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Goal 3: Advance Translational Research

Direct Upregulation of Antioxidant Defenses as a Therapeutic Strategy

Clinical trials involving administration of antioxidants such as vitamin C or vitamin E as therapeutic strategies for cardiovascular diseases associated with oxidant stress have proven to be surprisingly disappointing. A particularly attractive alternative approach is direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches. NRF2 is a master antioxidant and cell protective transcription ...more »

Submitted by (@jlombard)

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

Details on the impact of addressing this CQ or CC :

Direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches will avoid the well known caveats of drug-based approaches such as off target effects and detrimental side effects. Dietary supplements such as Protandim are already available; and beneficial effects of other NRF2 up-regulators such as resveratrol and sulforaphane are beginning to be recognized. The dietary approach is minimally invasive and has high preventative value.

Feasibility and challenges of addressing this CQ or CC :

Addressing this CQ is clearly feasible, as dietary supplements are currently available for humans, and the beneficial effects of foods containing compounds that upregulate the NRF2 system, e.g., broccoli, cauliflower, red wine, and grape juice are currently recognized. One challenge in addressing this question in animal models to date is that the only genetic model lacking NRF2 is a knockout mouse model, which have substantial limitations for in vivo physiological studies due to their small size. However, a recent R21 grant (#1R21OD018309-J. H. Lombard, P.I.) has allowed the development of a NRF2 knockout rat model which is better suited for physiological studies than the mouse model. In addition, the techniques used to develop the NRF2 knockout rat can be applied to multiple disease-sensitized strains, e.g., the Dahl salt-sensitive rat. Fawn Hooded Hypertensive rat, Obese Zucker rat, etc. Similar disease sensitized rodent genetic strains are not available in mice.

Name of idea submitter and other team members who worked on this idea : Julian H. Lombard

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2 up votes
7 down votes
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Goal 3: Advance Translational Research

Scientific priorities for HIV-related cardiovascular research

Millions of virally suppressed patients with HIV/AIDS survive to older ages and will become increasingly vulnerable to inflammation-associated cardiovascular disease. The critical challenge is to determine whether age-driven cardiovascular declines that occur HIV-infected people are exacerbated by the persistent systemic inflammatory drive that occurs in virally suppressed patients. Studies that document cardiovascular ...more »

Submitted by (@bgelman)

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

Details on the impact of addressing this CQ or CC :

The impact of this critical challenge would be to heighten the translational impact of HIV-related cardiovascular research. Key facets of this challenge are: 1) To give high priority to studies that use human tissue specimens that have been carefully annotated and biobanked, 2) To be certain that proposed studies employ tissue from age-appropriate comparison patients who were not HIV infected, and 3) To avoid giving undue credence to acute infection or in vitro infection models (as with tat and gp120 toxicology) that do not reflect immunologic and virologic mechanisms in virally suppressed patients. Millions of virally suppressed patients with HIV/AIDS survive to older ages, and become increasingly vulnerable to cardiovascular disease. Ischemia-related disease causes dysfunction especially in organs that depend on abundant blood flow such heart, brain and kidneys. All these organs are affected to some extent by persistent inflammation in virally suppressed HIV-infected patents. The compelling question/critical challenge is to determine whether age-associated cardiovascular changes are exacerbated by persistent mild systemic inflammatory drive that are found in blood vessels of virally suppressed patients. Studies that document the presence of cardiovascular changes in older infected people without controls, or in vitro models of acute infection, both do not address issues of high translational relevancy. Using human tissue specimens from age-appropriate controls does.

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

1) Obtaining well-annotated organ specimens from HIV infected and noninfected people is feasible. The National NeuroAIDS Tissue Consortium (NNTC) collection goes well beyond the CNS and includes heart, lung, kidney, gut, liver, spleen and other organs. Many of the organs specimens in the collection have been annotated with virological and immunological markers already.

2) Over 900 autopsies on HIV infected patients are banked by the NNTC and over 100 of these decedents were over the age of 50. Over 200 controls are effectively banked. These specimens and related clinical data are in the public domain at this time.

3) Age appropriate autopsies were done by the NNTC, and a large number of NIA sponsored tissue repositories have accumulated tissue from elderly patients.

Challenges:

1) The limitations of using autopsy material and the limits of a cross sectional view need to be better understood and appreciated. These studies should not be written off scientifically as "observational" or "not hypothesis driven."

2) The lessons of not using age-appropriate controls have NOT yet been learned in the HIV/AIDS research community. A prime example is an overabundance of brain aging surveys in HIV infected populations that did not contain age-appropriate controls. A controversial and inconclusive brain aging pathology literature was produced because of that.

Name of idea submitter and other team members who worked on this idea : Benjamin Gelman

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12 up votes
40 down votes
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Goal 2: Reduce Human Disease

National network to study the pathobiology of sepsis

Sepsis is the leading cause of death in hospitalized patients, the 3rd leading cause of death in all people in the US, the most common condition leading to widespread vascular collapse, among the most common causes of respiratory failure, and a frequent cause of acute cardiac dysfunction.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Developing a national network to address important aspects of sepsis (causes and consequences of cardiac dysfunction, molecular determinants of respiratory failure) and serve as a trials group for testing novel interventions for new discoveries.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

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2 net votes
4 up votes
2 down votes
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Goal 3: Advance Translational Research

Vascular disease awareness

Increase awareness of vascular disease in the population. Public recognition and understanding is poor, despite high prevalence. ­ Improve public education about vascular diseases, the risk factors, early signs, and treatment.

Submitted by (@societyforvascularsurgery)

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

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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1 net vote
2 up votes
1 down votes
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Goal 2: Reduce Human Disease

Vascular Origins of Cognitive Decline

A comprehensive research plan is needed to identify the vascular causes of cognitive decline, to develop early treatment options, and most ideally, develop effective measures to maintain cognitive function.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Reduction in the number of elderly with cognitive impairment would not only increase quality of life but would reduce health care costs. Research is indicating that the pathologic decline in cognitive function is complex and may involve multiple pathways of cardiovascular and metabolic origin.

Feasibility and challenges of addressing this CQ or CC :

Addressing this issue requires research on vascular biology, tools for brain imaging and measurements of cognitive decline, all of which are advancing in development and implementation. The 2013 BRAIN Initiative includes $100 million in commitments from 5 federal agencies, including $46 million from NIH in grant awards focusing on new tools and techniques.

The frequently observed cognitive decline with aging can occur in a mild state or can progress to forms of dementia that are devastating to individuals and families and require a functioning and affordable support system for the affected individual. The vascular origin of this decline is only beginning to be understood. With increasing numbers of the US population surviving to their 80s and 90s, healthy cognition is critical for these elderly to be able to live independent functioning lives. .

 

As always commitment of funds is required as well as identifying appropriate research populations and efficient study designs.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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30 net votes
51 up votes
21 down votes
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