We propose to characterize the etiology and natural history of rare and uncommon diseases, both known and unknown that present with symptoms and signs associated with the risk of overt or potential cardiovascular dysfunction. We will also study rare genetic modifiers and identify novel disease mechanisms contributing to common cardiovascular diseases. In so doing, we will expand our knowledge about these disorders and provide access to subjects of interest for research, teaching, and clinical experience. Individual subjects seen under this protocol may initiate the establishment of specific disease-related protocols involving intensive natural history studies, disease discovery and potential innovative therapeutic studies. In addition to its role in investigating individuals who are of interest to the Cardiovascular and Pulmonary Branch (CPB) and the Center for Molecular Medicine (CMM) of the NHLBI, this protocol can provide a possible avenue for admitting subjects from other NIH programs such as the NIH Undiagnosed Diseases Program, the Center for Human Immunology Trans-Institute program or other NIH protocols where subjects exhibit cardiovascular features.
A caloric restricted diet has numerous health effects including the reduction in numerous cardiovascular disease risk factors. The cellular programs activated by caloric restriction are similarly turned on in preclinical studies in response to a 24-hour fast. We found that a beneficial effect of a 24-hour fasting blunted the activation of a component of the immune system, termed the NLRP3 inflammasome, which is associated with the development of diabetes and atherosclerosis. This clinical protocol was developed to study this inflammasome in human blood cells to evaluate whether the beneficial immune effects of fasting/caloric restriction are operational in humans. Blood samples to test the immune response were collected in subjects after a fixed caloric meal and in response to a 24-hour fast (water intake was not be restricted). The objective of this pilot study was to identify if these immune adaptive pathways can be activated in human subjects as a possible readout to test whether this pathway could be investigated as a therapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases such as diabetes and/or atherosclerosis.
Psoriasis causes chronic inflammation in the body. Our study will explore if a kind of vitamin B3 dietary supplement, nicotinamide ribosome can improve immune system function in the blood and skin of people with mild to moderate psoriasis. This in turn may lead to more treatment options. Eligible participants may call the Office of Patient Recruitment at 1-800-411-1222.