Goal 1: Promote Human Health

To expand knowledge of the molecular and physiological mechanisms governing the normal function of heart, lung, blood, and sleep systems as essential elements for sustaining human health.

Goal 1: Promote Human Health

Microbiome, immunity and health

What is the influence of the microbiome on the immune system and other development processes across the normal human lifespan?

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 :

There is a potential of microbiome-based therapeutics to treat human disease. A deep understanding of the mechanisms governing the interactions between microbiomes, immune development and metabolic networks are key to improve health outcomes. New therapeutic approaches including personalized pre- and probiotics and nutritional interventions, narrow spectrum antibiotics and fecal transplantation therapies may provide an avenue for safer alternatives to traditional clinical interventions for chronic diseases.

Feasibility and challenges of addressing this CQ or CC :

Through the Human Microbiome Project investigators have started to characterize and analyze the microbial communities in the body. Today metagenomics tools and other technologies developed through these projects are available to the broader scientific community. Such tools and standardized protocols can be applied and improved in future research to address functional and mechanistic consequences of host-microbiome interactions and their influence in human health.

Bacterial communities colonize the human host from birth, giving rise to a highly adapted microbiota that is established, but dynamic, in healthy individuals though life. Growing evidence suggests that this complex symbiotic relationship between microbiome and its host fulfills critical physiological roles, immune maturation, and diverse metabolic functions. Immune maturity and balance is conquered and maintained partly due to the influential interaction among the resident gut microbiota and host mucosal immune system. In addition, the immune system is continuously stimulated by chronic systemic viruses; the human virome is considered one of the drivers of idiopathic systemic inflammation that has been linked to many of the most severe public health threats, including cardiovascular diseases. In depth understanding of the underlying mechanisms that control homeostasis and dysbiosis (microbial imbalance) of the gut, lung and/or other host microbiota are vital for our ability to potentially manipulate the microbiota to achieve positive clinical outcomes for systemic diseases.

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

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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

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15 net votes
25 up votes
10 down votes
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Goal 1: Promote Human Health

Reduce burden of vascular disease

How can we reduce the burden of vascular disease by promoting healthy lifestyle including diet, exercise, and smoking cessation?

Submitted by (@societyforvascularsurgery)

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

Details on the impact of addressing this CQ or CC :

­Conduct community level and scale studies in higher risk populations, identify effective tools to achieve healthy lifestyle and prevent or retard the progression of vascular disease. Determine which interventions work.

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

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0 net votes
1 up votes
1 down votes
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Goal 1: Promote Human Health

Understanding Plasma Triglyceride Metabolism

Understanding basic mechanisms for intravascular triglyceride metabolism

Submitted by (@sgyoung)

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

Details on the impact of addressing this CQ or CC :

Over the past two years, it has become extremely clear that impaired processing of triglyceride-rich lipoproteins has an enormous impact on the frequency of coronary heart disease. For example, large genetic studies have shown that loss-of-function mutations in the gene for apolipoprotein CIII protect from atherosclerotic heart disease. Equally important is the observation that mutations in the gene for apolipoprotein AV are nearly as important as the LDL receptor as a cause of coronary heart disease.

 

The fact that plasma triglyceride metabolism is so important for atherosclerotic heart disease has caught the field by surprise. For many years, there was considerable doubt about the importance of plasma triglycerides for atherosclerotic heart disease. These doubts have vanished.

 

Now, in terms of basic research, the triglyceride metabolism field needs to play "catch up" ball. At this time, we have little understanding of intravascular lipolysis. We don't really know the molecular basis for the effects of apo-CIII, apo-CII, and apo-AV on intravascular lipolysis. The effects of these proteins on the LPL–GPIHBP1 complex are unknown. We don't understand how the lipid products of lipolysis move across capillary endothelial cells. We don't even understand why heparin releases LPL from GPIHBP1, and that observation is more than 60 years old! We don't understand the factors that explain differences in the efficiency of plasma triglyceride metabolism.

Feasibility and challenges of addressing this CQ or CC :

I believe that the field is now poised to understand intravascular lipolysis at the molecular level, and to investigate why some individuals have inefficient lipolysis and higher plasma triglyceride levels. Within the past few years, the "cast" of molecules that affect (or regulate) plasma triglyceride metabolism have come into focus. The field is poised for progress.

 

In part because of long-held doubts about the importance of plasma triglyceride metabolism, reagents for key proteins in intravascular metabolism are not in hand simply not in hand (recombinant proteins, specific antibodies). Developing and distributing these reagents is quite feasible, but it has not yet been accomplished.

 

Similarly, imaging tools are now available to understand the movement of the fatty acid products of lipolysis to myocytes and adipocytes, but there have been few attempts to use those tools.

 

We need to understand intravascular metabolism. At this time, no one understands the basics. No one knows how app-CII, app-CIII, and app-AV work. We need to understand how ANGPTL4 and ANGPTL3 regulate lipolysis. We need to understand the biochemistry of the LPL–GPIHBP1 complex. These tasks are feasible but will require hard work from many interested investigators.

 

In the end, once intravascular lipolysis is better understood, it is highly likely that there will be many new strategies for lowering plasma triglyceride levels and reducing the frequency of coronary heart disease.

Name of idea submitter and other team members who worked on this idea : Stephen G. Young

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0 net votes
7 up votes
7 down votes
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Goal 1: Promote Human Health

Individually-Tailored Approaches to Manage Perinatal Weight Gain to Improve Maternal and Infant Health

Managing perinatal weight gain is a major challenge in research and practice. More women enter pregnancy already overweight or obese which increases the risks for morbidity and mortality for both mother and baby. Novel strategies are needed to effectively manage weight gain in this population. This may include infusing engineering principles and dynamical modeling to better understand the complex interactions of biological ...more »

Submitted by (@dsd110)

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

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24 net votes
34 up votes
10 down votes
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Goal 1: Promote Human Health

Evaluation of large-scale regulatory efforts in the US and elsewhere

A number of cities(e.g Berkeley), states and countries (e.g Mexico's SSB tax, Chiles SSB and soon marketing controls and food package front of package label) will go into effect. Rigorous evaluations of the efforts will provide some sense of their potential to effect food purchase and dietary pattern and ultimately cardiometaboiic changes. Serious rigorous independent evaluations are needed to learn if these options--pushed ...more »

Submitted by (@popkin)

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

Details on the impact of addressing this CQ or CC :

We must learn what we can from the natural experiments not only in the US but globally about both the effects of these efforts on food industry behavior as well as household and individual food purchases and dietary patterns and subsequently their effects on obesity and key cardiometabolic outcomes. This requires serious rigorous teams of scholars to utilize a combination of commercial data sets on food purchases, individual diet, body composition measures of obesity and fat composition and biomarkers.

Feasibility and challenges of addressing this CQ or CC :

These efforts are occurring and will be accelerating across many countries in Asia and Latin America. At the same time many cities or states in the US are moving to implement limited sets of key changes. There is a pressing need to learn if these efforts truly will matter and what changes would be needed to enhance their impact, if any. Finding large-scale regulatory ways to reduce improve our diets, prevent/reduce the prevalence of obesity and all the diet and obesity-related NCD's is critical.

Name of idea submitter and other team members who worked on this idea : Barry Popkin

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22 net votes
42 up votes
20 down votes
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Goal 1: Promote Human Health

Microbiome and hypertension

What is the connection between the gut microbiome and the development of hypertension?

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Help understand the normal and pathophysiology of human hypertension and related disorders, such as metabolic syndrome, diabetes, obesity, and stroke.

Feasibility and challenges of addressing this CQ or CC :

Yes., this is feasible.

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

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7 net votes
25 up votes
18 down votes
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Goal 1: Promote Human Health

Cardiac Gene Networks

What is the level of intra-tissue variation of cardiac development gene regulatory networks at single cell resolution?

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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2 net votes
16 up votes
14 down votes
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Goal 1: Promote Human Health

Brain-Heart Connections

Depression and CHD will become the 2 leading causes of disability in the next decade. Chronic as well as traumatic stress increases CVD risk by about 50%. Although we understand that there are connections between psychosocial stress, affective disorders, and CVD, we do not understand the vast array of brain areas that impact the CV system and the mechanisms connecting them. Neuroscience has made great leaps in understanding ...more »

Submitted by (@cshively)

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

Details on the impact of addressing this CQ or CC :

For example, we still do not have a comprehensive understanding of how depression increases incident CHD.

 

Alternative treatments for depression are needed that target disrupted pathways known to promote CVD (e.g. autonomic, inflammation).

 

What are the mechanisms through which PTSD doubles incident CHD within a decade?

 

What are the mechanisms through which exercise, sleep, and certain diet patterns mediate the effects of psychosocial stress on health?

 

Not all stressed people get CVD and some data suggests that coping style mediates stress effects on CVD risk. If so, perhaps we can teach coping styles. But to do so we need to know more about whether and how certain coping styles modulate stress effects on the CV system.

 

A major cause of psychosocial stress in modern America is social density. The higher the density, the less tolerance there is for deviance from the norm. How does increased social density effect CV physiology? Are there ways to intervene through spatial partitioning or interaction patterns that alter perceptions of crowdedness or lack of privacy?

Feasibility and challenges of addressing this CQ or CC :

We have all the tools to address this over-arching area and these specific questions. They just need to be made a priority.

Name of idea submitter and other team members who worked on this idea : Carol Shively

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9 net votes
14 up votes
5 down votes
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Goal 1: Promote Human Health

Mechanism of dietary polysaccharide/ sugars in averting CVD and cancer

CQ

Submitted by (@mayaraman)

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

Details on the impact of addressing this CQ or CC :

Non-communicable diseases and their preventive measure are always of interest. But we always, face side-effects because of these new applications. And at times, these techniques fail.

Diet today is a attractive area of discussion. Everyday, we read or hear that control of diet has cured severe conditions.

In fact, as the saying goes, we are what we eat. Today, scientific communities can lay emphasis on the researches concerning these topics. Dietary polysaccharides/ polyphenols etc. have a promising role in deciding our health. We can include these in our diet but the mechanism of the action of these factors in preventing diseases has not be explored in detail. The role of specific factors in diet at specific sites, may assist in pin-point treatment with better results and no side-effects. Can this topic be considered for research!

Feasibility and challenges of addressing this CQ or CC :

Challenges include creating teams of researchers with basic research expertise and experienced researchers to collaborate and come up with plans to understand the action of system and to design strategies utilizing dietary carbohydrates to have healthier and long term benefits.

Name of idea submitter and other team members who worked on this idea : Raman M

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-8 net votes
6 up votes
14 down votes
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Goal 1: Promote Human Health

Promoting the Development of Animal and Cellular Model Systems

NHLBI might consider creating incentives for the development of core labs and national facilities to promote development of animal and cellular model systems that mimic lung injury, repair, and regeneration.

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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3 up votes
4 down votes
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Goal 1: Promote Human Health

Extreme makeover: harnessing adaptation mechanisms for therapy

What extreme adaptive physiological mechanisms in heart, lung, and blood systems might have the greatest potential to be targeted or employed in therapeutic strategies? Human physiology, including the heart, lung and blood systems, is known to possess extreme adaptive mechanisms to counter extreme conditions or unusual situations. Although some studies are being done, many of these mechanisms have not been fully explored ...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 :

May lead to new therapeutic strategies for HLB diseases. May improve our understanding of HLB physiology and adaptation.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to ask specific questions about adaptation mechanisms under extreme conditions and develop experiments to test them. This can be done in various experimental models as well as in humans.

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

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-4 net votes
8 up votes
12 down votes
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