Showing 2 ideas for tag "microcirculation"

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 »

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

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Goal 3: Advance Translational Research

New Targets for the Treatment of Heart Failure

Heart failure (HF) is one of the major health challenges in the 21st Century. Its prevalence is due a growing number of patients who survive heart attacks, who later develop heart failure; and the high incidence of diabetes leading to diabetic cardiomyopathy. Current treatments for HF only slow the progression of the disease; no treatment stops or reverses this adverse sequence. These limitations provoke the question... 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

The current treatment regimens for patients with heart failure (HF) focus on strategies to reduce cardiac work (by reducing heart rate, beta-blockers), afterload reduction (ACE inhibitors), and decrease in preload/blood volume (ACE inhibitors, aldosterone antagonists, diuretics). None of these treatments stop or reverse the progression of the disease. A recent gene therapy trial designed to improve cardiac contractility and calcium handling in HF has failed in clinical trials. Perhaps the reason that the current and experimental treatments have not produced an outcome of stopping or reversing the progression of the disease relates to the "cell" they are targeting. In this regard, the current treatments principally target cardiac myocytes, but there is evidence that vascular perfusion abnormalities may also be involved in the disease. One such piece of evidence relates to the diffuse fibrosis occurring in the failing hearts. Such fibrosis is often referred to as replacement fibrosis in that the fibrotic tissue has replaced cardiac myocytes which died. This death could be the result of a perfusion abnormalities caused by inadequate dilation of the coronary resistance vessels. Thus, is heart failure a pathology involving both the coronary circulation and cardiac muscle? In this regard, future investigations of heart failure consider cardiac-coronary interactions leading to perfusion abnormalities as a key factor in the progression of heart failure.

Feasibility and challenges of addressing this CQ or CC

The challenge of addressing a coronary vascular contribution to heart failure would involve an interdisciplinary approach using genetic models with cardiac and/or vascular (smooth muscle and endothelium) expression or knock-out of key genes involved in cardiac function and vascular control. Sophisticated measurements of cardiac function and metabolic status of the heart using echocardiography, MRI, PET and a L-Band EPR would provide insight into flow-function-metabolism-oxygenation relations in the normal and failing heart.

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

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