What is the effect of sleep disorders on child development? Specifically, how sleep apnea with intermittent hypoxia and or sleep deprivation alters the normal trajectory of maturation of brain regions controlling cognition, behavior and the cardiovascular system?
BMP9 circulates in the blood and signals through the endothelial cell. IN the absence of Alk 1, such as in HHT, the vessels become over-active. The overactivity can be partially balanced by activation of a second signaling pathway: notch. Would targeting notch be a useful drug target to reverse AVM formation
Alk 1 or Endoglin deficient endothelial cells promote recruitment of monocytes/macrophages and differentiation of them can play a critical role in development of arteriovenous malformations. Will targeting macrophage recruitment or activation instead of angiogenesis result in greater understanding leading to new therapeutic targets to control disease?
Endothelial cells derive from cells in the bone marrow. Circulating precursor endothelial cells contribute to newly forming vessels.
Do Alk 1 and/or Endogln mutations affect the functions of these cells once they incorporate into growing vessels. These vessels then go on to form arteriovenous malformations
Liver arteriovenous venous malformations creates a high flow shunt that over time creates high output cardiac failure with no effective treatments.
Heart Failure (HF) remains a major public health burden. A working group was convened by NHLBI and ODS in June, 2013 to address the role of diet and nutrition in management of HF. A review of existing evidence produced no clear rationale for appropriate dietary interventions. On the contrary, the group developed recommendations for conducting additional research specifically on the role of sodium, fluid, nutrients, and ...more »
Provide resources and training to improve the ability of scientists to bridge the “translational gap”. Continue and expand the VITA program.
There are many novel imaging modalities, including radiographic, scintigraphic, sonographic, MR-based, and molecular for the heart and vessels. Patients have unique medical "signatures"- genetic risk factor profiles, epigenetic markings, "omics" profiles, and personal clinical and family history as well as symptom constellation and physical exam findings. Can these all be integrated into a single personalized profile ...more »
The majority of patients who are resuscitated from OHCA have a presumed cardiac etiology. One of the key interventions post cardiac arrest is to study the coronary circulation for underlying thrombosis. Some centers do this routinely but at other centers interventional cardiologists are hesitant to do this since the mortality rates are high and so affect their individual and institutional performance measures related ...more »
Identification of new genetic/genomic variants and risk genes often opens a new window to explore the fundamental molecular mechanisms underlying a disease and to develop new methods and strategies for diagnosis and treatment. Existing genomic variants and/or mutations explain only 10% to 20% heritability of common heart diseases. Much remains to be done in this important area. However, most genetic projects are discovery-driven ...more »
What are the molecular phenotypic differences in blood and tissue of IPF ILD and how do they relate to disease course and potential response to therapy. There is a need to gain understanding in humans of the differences and similarities in iPF and iLD in general to eliminate the idiopathic nature and establish human targets. The challenge is coupling such research to longer term studies/outcomes and potentially clinical ...more »
Prevention trials, implemented to reduce or delay progression to overt disease in a population at risk to the disease, are an important approach to health promotion. Therapies shown to reduce disease severity in patients with a specific disease are obvious, but not the only, candidates for a prevention trial in populations at high risk for prevalent diseases (such as heart failure, diabetes, COPD, asthma in children). ...more »