Mechanistic transducers and biomarkers of sedentary behavior-associated cardiovascular disease risk in Latina women

Mechanistic transducers and biomarkers of sedentary behavior-associated cardiovascular disease risk in Latina women Mechanistic transducers and biomarkers of sedentary behavior-associated cardiovascular disease risk in Latina women The Basic Science Project will assess biomarkers by which sedentary behavior (SB) may promote cardiovascular disease (CVD) risk and impair healthy aging. Our model is that extensive sitting causes perturbations in mitochondrial and endothelial dysfunction via sub-optimal blood flow and reduced muscle engagement in the lower extremities. These perturbations influence biomarkers and transducers of CVD risk. The Basic Science Project will leverage biospecimens and biomarker and behavior data generated in Clinical Project to evaluate known and novel associations of SB with CVD risk in postmenopausal Latina women. We hypothesize that CVD risk biomarkers, including biomarkers of glucoregulation and lipid metabolism, mitochondrial and endothelial functioning, will improve after reductions in sitting time. Aims 1 & 2 will compare 3-month outcomes of an intensive 25%-reduced sitting time intervention vs. a control healthy advice condition on CVD- and aging-related biomarkers. AIM 1 NOVEL BIOMARKERS. 1a. Mitochondrial function. Targeted, plasma metabolomics (e.g., amino acids, acylcarnitines). 1b. Epigenetic DNA methylation (Next Generation Sequencing (NGS)) profiling of white blood cells to determine bio-age and Apparent Methylomic Aging Rate. 1c. Epigenetic, circulating microRNA profiling (NGS) and in vitro validation of candidate cell-cell communication transducers. AIM 2 STANDARD BIOMARKERS. 2a. Endothelial function. Plasma immuno-assay of inflammation (CRP), endothelial cell activation (VCAM1, ICAM1, P- and E-selectins), oxidative stress (F2-isoprostane), and coagulation (fibrinogen). 2b. Glucose and lipid metabolism. Standard assays of fasting plasma insulin, glucose, and lipid panel and on hemoglobin A1c (HbA1c). SUMMARY: The Basic Science Project will assess standard and novel candidate biomarkers (mitochondrial metabolites, epigenetic factors) of CVD risk and shed light on basic, biological mechanisms not evaluated previously in SB research. Mechanistic transducers and biomarkers of sedentary behavior-associated cardiovascular disease risk in Latina women The Basic Science Project aims to identify the mechanistic transducers and biomarkers of sedentary time-associated cardiovascular disease risk in Latina women. It is one of three Projects focused on sedentary behavior in Latinas that make up the UCSD Womens Cardiovascular Health Research Center, which includes a Clinical Project, Population Project, and Training Core. For the proposed subaward part of the Basic Science Project, I will continue to provide executive and scientific leadership, direct study design and execution, provide oversight of clinical laboratory activities at the South Bay Latino Research Center (Chula Vista, CA) site of the Clinical Science Project, direct all biomarker analyses, data analysis and interpretation, lead preparation and serve as corresponding author on all manuscripts generated from the project, and assure dissemination of findings. I originally conceived of and wrote the project proposal and have been the Basic Science Project Lead prior to this subaward. Dr. Brinda Rana will be the UCSD Administrative Site PI of the Basic Science Project.