Goal 1: Promote Human Health

Mechanisms of Vascular Stiffness

Increased vascular stiffness has been identified as an important cardiovascular event that accompanies aging and cardiovascular disease. Although multiple vascular changes have been identified and suggested to cause increased vascular stiffness, our understanding of the underlying mechanisms needs to be refined in order to develop useful therapeutic strategies to prevent or reverse these changes. An example of critical ...more »

Submitted by (@meiningerg)

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

Details on the impact of addressing this CQ or CC :

Ultimately, addressing this CQ would impact treatment of CV disease, reduce incidence of significant and life threatening CV events and improve quality of life. This area of investigation is relevant to therapeutics and potentially lifestyle changes that will improve CV health and slow CV age related changes linked to disease.

Feasibility and challenges of addressing this CQ or CC :

Current advances in our technologies make it very feasible to address new questions to improve our knowledge of the mechanisms underlying vascular stiffness. Challenges will include developing multi-scale and cross disciplinary strategies that will, by design, facilitate an integrated understanding of the process leading to altered vascular stiffness.

Name of idea submitter and other team members who worked on this idea : Gerald A. Meininger

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55 net votes
88 up votes
33 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
0 down 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 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 2: Reduce Human Disease

How gene mutations contribute to defects in vascular development

How do gene mutations in endoglin and alk 1 create arteriovenous malformations leading to disease. Alk 1 and endoglin are receptors in TGFB/BMP family signaling. TGFB/BMP have roles in vascular development, remodeling and maintenance in vascular integrity. Understanding the downstream effect will lead to advancements in reducing genetic diseases such as HHT as well as vascular malformations in general

Submitted by (@mariannes.clancy)

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 : Marianne Clancy MPA, Chris Hughes PhD

Voting

3 net votes
3 up votes
0 down 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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-5 net votes
2 up votes
7 down votes
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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does "goal-targeted" therapy (with adjustments/additional therapy, if certain "goals" are not achieved) improve quality of life, functional status, and survival in patients with pulmonary arterial hypertension? Trials of therapies for hepatopulmonary syndrome.

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges 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

Voting

2 net votes
2 up votes
0 down votes
Active

Goal 1: Promote Human Health

New Approaches to study interactions of blood cells with components of the vascular wall

To eventually modulate pathologic communication processes employing new therapeutics, there is a need to better understand the transcellular communication between blood cells and components of the vascular layer in vivo.

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

A better understanding of this largely unrecognized and underappreciated form of transcellular communication would allow us to use the information to not only detect disease at its very earliest stages, but perhaps also modulate pathologic communication processes employing new therapeutics.

Feasibility and challenges of addressing this CQ or CC :

It is now feasible to address this CQ because of the availability of techniques such as atomic force microscopy, multi-photon intravital microscopy, computational and experimental approaches.

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

Voting

15 net votes
25 up votes
10 down votes
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Goal 2: Reduce Human Disease

Understanding the Role of the Vasculature in Dementia

Dementia is traditionally grouped into vascular dementia, Alzheimer's dementia, Parkinson's dementia and other causes of dementia. Vascular dementia is generally thought to be a consequence of strokes but there are some recent studies indicating that even Alzheimer's dementia may have a vascular underpinning. Vascular permeability is increased in the early stages of Alzheimer's disease and it is possible that similar ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

The NHLBI could fund programs which enable vascular biologists to collaborate with neuroscientists and neurologists in order to understand whether the vasculature has a causal role in the progression of dementia.

 

 

 

Can interventions that improve vascular function prevent the progression of dementia? Instead of using broad interventions such as statins which affect numerous signaling pathways, vascular biologists could target selected aspects of vascular health such as improving vascular barrier function and vascular regeneration.

 

If these interventions that have been shown to be efficacious in other vascular beds outside of the brain are also effective in the brain, then important new therapies could be developed for dementia which is likely to become one of the leading cause of death in the next decades.

Feasibility and challenges of addressing this CQ or CC :

A key challenge for targeting the brain vasculature will be the blood-brain barrier. Understanding the role of the blood-brain barrier in dementia will be a prerequisite to developing novel vasculature-directed therapies.

Name of idea submitter and other team members who worked on this idea : Jalees Rehman

Voting

9 net votes
13 up votes
4 down votes
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Goal 1: Promote Human Health

Intersecting Developmental Biology with Vascular Physiology and Biology

Although many think of the vasculature as a lump sum of vessels that all react in a similar fashion to a certain stimulus, e.g., alpha-adrenergic activation, this is not the situation. For example, coronary resistance vessels show little to no direct response to alpha-adrenergic activation while resistance vessels in most organs show marked constriction. Another example is the response of different vessels to angioplasty ...more »

Submitted by (@wchilian)

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

Details on the impact of addressing this CQ or CC :

A challenge facing many specialists in vascular medicine, vascular surgery, and cardiology is understanding the ramifications, and the basis, of the vascular pathology in the context of the organ system. Another way of re-stating this as a question is: Are the unique attributes of the vascular biology, pathology and physiology of a particular organ system connected to specific aspects of development. This question would help both the basic on clinical scientists understand the basis of why a blood vessel in the kidney may be different than one in the heart, or in the brain with the goal of devising more selective therapies to approach vascular disease in specific organs. Scientists in the area of vascular development have long appreciated that vascular cells in different organs arise from different embryological origins; yet how this information translates into the intricacies of vascular control, or responses to pathology is not resolved. Understanding the basic biological mechanisms of how the embryological source of the vasculature affects pathology and physiology could engender treatment of vascular disorders.

Feasibility and challenges of addressing this CQ or CC :

This idea could be implemented by encouraging multi-PI efforts from vascular developmental biologists, and investigators engaged in studies of microvascular control mechanisms and/or vascular biologists interested in vascular pathologies such as restenosis and vascular lesions. Advances in fate mapping techniques have enabled developmental biologists to track embryological origins of cells into specific organ systems into adulthood. With such a multi-faceted approach a better understanding of vascular physiology and pathophysiology will be obtained that hopefully will be translated into more effective treatments.

Name of idea submitter and other team members who worked on this idea : William M. Chilian

Voting

15 net votes
26 up votes
11 down votes
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Goal 4: Develop Workforce and Resources

Develop Vascular Anomalies Medical Training and Research Programs

Patients with vascular anomalies frequently see many physicians and undergo extraneous tests with incorrect diagnoses. A major reason for this is due to the fact that medical training does not include Vascular Anomalies in the syllabus. Thus, many specialties erroneously use the term "hemangioma" for any vascular diagnosis. Over the past 2 decades, there have been major breakthroughs in basic and genetic research, as ...more »

Submitted by (@fblei0)

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 training program for vascular anomalies will facilitate improved, more efficient and meaningful patient care. It will also engender collaborative research and data collection for these patients.

Feasibility and challenges of addressing this CQ or CC :

This is very feasible. There are key individuals, advocacy groups, and programs in each of the disease entities - Hemangiomas of infancy, Syndromic Vascular Anomalies (CLOVES, Sturge Weber, Proteus, Maffucci, Klippel Trenaunay, Cutis Marmorata, PTEN Associated Hamartoma Syndrome, Lymphedema Syndromes, etc) which would benefit from a coordinated strategic plan to pool resources, develop a data bank and tissue bank and foster collaborations to move this field forward. This could also serve to develop a network of tiered Vascular Anomalies Programs with certification.

Name of idea submitter and other team members who worked on this idea : Francine Blei, MD

Voting

-1 net votes
7 up votes
8 down votes
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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does treatment with spironolactone improve outcomes in patients with pulmonary arterial hypertension (and/or pulmonary hypertension associated with diffuse parenchymal lung disease or COPD)? Spironolactone has been shown beneficial in CHF and many of the same mechanisms are at plan in RV failure from pulmonary hypertension. Again, no clear evidence whether this is a useful treatment or not, and no evidence to guide ...more »

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges 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

Voting

2 net votes
2 up votes
0 down votes
Active