evoc - evs in obesity and cardiometabolic disease

Conditions: Cardiovascular Diseases

Summary: the goal of this observational study is to research the impact of molecular signals from the heart, liver and fat tissue on cardiovascular disease risk, and the presentation of type ii diabetes and diseases that affect the heart, blood vessels and metabolism (cardiometabolic disease). specifically, the focus is on the content and function of extracellular vesicles (evs), small sacs released from a cell's surface that contain important molecular cargo. the main questions it aims to answer are: 1. what molecular cargo do adipose-tissue evs carry? 2. how do these cargo impact cardiac and hepatic function? 3. are changes in ev content related to cardiac function and adiposity with weight loss? tissue samples from fat tissue and blood samples will be collected from patients receiving bariatric weight loss surgery.

the primary clinical objective of this research is to study the impact of molecular signals from the adipose tissue to the heart, liver and brain on cardiovascular disease risk in obesity, type ii diabetes and other metabolic diseases that affect the heart, blood vessels and metabolism (cardiometabolic disease). specifically, the focus is on the content and function of extracellular vesicles (evs), small sacs released from a cell's surface that contain important molecular cargo. the hypothesis is that evs derived from metabolically active fat tissue located around the abdominal organs (visceral adipose tissue) have a different cargo than those derived from non-metabolically active fat tissue located directly under the skin (subcutaneous adipose tissue), and that these cargoes impact the function of other organs. further, we hypothesize that visceral adipose evs are also present in the plasma in circulation, and that the content changes as patients become metabolically healthy following bariatric surgery. after obtaining patient consent, samples from visceral fat tissue, subcutaneous fat tissue and blood will be collected during the gastric bypass weight loss surgery. these samples will be brought to lab where they will be processed for evs. subject's medical history and records will be followed as well. an optional, secondary blood draw may be collected 3 month post-surgery or within 24 months. following collection, the samples will be brough to the laboratory of the pi for processing. samples will undergo characterization for proteins, extracellular or exosomal rnas, tissue rnas (e.g., leukocyte/buffy coat), and/or metabolites. a trascriptomic and proteomic analysis will be performed to determine differences in protein and rna expression. the evs will be extracted from subcutaneous and visceral fat tissue and used to treat heart muscle cells and liver-on-chip cells that have been produced in a laboratory setting.

Eligibility criteria:
inclusion criteria: * age greater than or equal to 18 years of age * obese (bmi\>/=30 kg/m2; for obesity/bariatric surgery group) * for 30 patients, additional criteria will be presence of pre-diabetes or diabetes (hgba1c \> 5.7 or fasting blood glucose \> 100). * provision of written informed consent exclusion criteria: * pregnancy (as adjudicated by patient history) * prior clinical history of myocardial infarction or valvular heart disease

Keywords: extracellular vesicles cardiometabolic disease cardiovascular risk type ii diabetes