Addressing this line of research could define biomarkers and pathways useful for prediction of how human response to an external stimulus of varied nature (i.e. microorganism, chemical, physical) could lead to specific outcomes in relationship to the duration of the exposure and the genetic makeup of the individual exposed. Identification of early signals and the pathways involved could lead to novel preventative or therapeutic approaches.

Methods for systems biology approaches to address complex pathobiological iterations are ready to be exploited to answer these questions.
Great progress has been made in the clarification of basic mechanisms of molecular and cellular response to environmental stimuli, in cross-sectional analyses. The continuum of the response in relationship to the genetic background of individuals responding with a homeostatic or pathological long-term outcome is missing from these data.

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?

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

The vasculome is comprised of a vast network of vessels that globally interacts with all of the other organ systems within the body. Disorders of the vasculature have a significant adverse effect on those organ systems and are a major source of mortality and morbidity. Systematic mapping of vasculome expression will reveal disease causality patterns that have thus far been unobserved.

The tools are available, the coordination is not. The NHLBI and VBHB have the expertise, the experience, and the leadership necessary to oversee the multiple studies, date collections, and organizational systems needed for mapping the vasculome.

Blood pressure monitoring via a pressure cuff has been shown to miss many of the problems with elevated blood pressure (e.g. morning surge, normotensive salt sensitivity). Continuous monitoring of blood pressure while measuring micro-capillary health will enable feedback control of the inflammatory events surrounding hypertension, salt sensitivity and related diseases.

At least three companies are producing research grade products for wearable continuous blood pressure monitoring. The Qualcomm X Prize has yielded several technologies that could continuously monitor microvascular health (e.g. inflammation). We have developed a genetically driven decision tree that will enable physicians can classify their patients into one of 6 cardiovascular types. Each type has a personalized therapy, many of which rely on dietary instead of pharmaceutical treatment. Thus, we need to move cardiovascular diagnosis and therapies into the modern wellness age of medicine.

As an example, recent studies suggest key regulatory roles of RNAs (e.g., microRNAs and long non-coding RNAs) in cardiac pathological hypertrophy and heart failure. Better understanding of such mechanisms will spur development of new therapies based on these mechanisms.

Most of the infrastructure and methods are in place. There appears to be growing interest and excitement about the potential of this research area. However, this field needs more researchers.

Increase and gain novel understanding of heart, lung, and blood physiologic systems

Emerging technologies, databases and merging of disciplines in the context of big data has the potential to make this feasible in the next 5-10 years

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

Funding an initiative would challenge the community to explore the issues related to the aging CHD community and the combination of physical and emotional stresses. Once the data are available, it may open new areas of targeted healthcare and medicine.

This community continues to grow, age, and we could only hope they continue to enjoy good health and improved function in our society.
So often RO1's and other grant mechanisms have a singular disease focus approach to a cohort, but this growing and aging population is influenced by more than one concern. Medically, there are common chronic conditions like cardiovascular disease and obesity (with all their concomitant issues), and newer issues such as family and child bearing, quality of life related to employment, social inclusion/exclusion, and the aging of the caretakers.

The VTE field is approaching a new era of therapy in which predictive measures at the primary care level will identify those patients most at risk for VTE. With the identification of predictive biomarkers for VTE occurrence, efforts will be necessary to develop point-of-care or in-home biomarker testing devices to improve risk-assessment scoring and identification, so that patients could then be treated before progression. It will also be critical to accelerate risk-scoring systems that are beginning to incorporate biomarker candidates into the algorithm for use in clinical trials. Studies that will focus on correlating risk-assessment scores and biomarker research findings will provide a more accurate risk prediction and diagnostic value.

While we are fully supportive of the recent emphasis on patient‐centered outcomes and implementation science, we are also reminded of the critical importance of investigating underlying mechanisms of pulmonary, critical care and sleep disorders. Recent discoveries have created exciting progress in the areas of cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and biological therapies in asthma. Only through further efforts to elucidate underlying mechanisms are new therapeutic approaches likely to emerge. Promoting further academic‐industry interactions are likely to yield benefits, which will ultimately lead to improvements in the health of our nation.