Faculty Bibliography

Macrophages represent one of the most numerous and diverse leukocyte types in the body. Furthermore, they are important regulators and promoters of many cardiovascular disease programs. Their functions range from sensing pathogens to digesting cell debris, modulating inflammation, and producing key cytokines and other regulatory factors throughout the body. Macrophage research has undergone a renaissance in recent years, which has propelled a newfound interest in their heterogeneity as well as a new understanding of ontological differences in their development. In addition, recent technological advances such as single-cell mass-cytometry by time-of-flight have enabled phenotype and functional analyses of individual immune myeloid cells, including macrophages, at unprecedented resolution. In this Part 1 of a 4-part review series covering the macrophage in cardiovascular disease, we focus on the basic principles of macrophage development, heterogeneity, phenotype, tissue-specific differentiation, and functionality as a basis to understand their role in cardiovascular disease.

RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN. Twenty-five genes, including LRP11 and PLIN5, had editing sites that were associated with plasma lipid levels. Our findings provide new insights into the genetic regulation of RNA editing and establish a rich catalogue for further exploration of this process.

Cardiovascular health is a primary research focus, as it is a leading contributor to mortality and morbidity worldwide, and is prohibitively costly for healthcare. Atherosclerosis, the main driver of cardiovascular disease, is now recognized as an inflammatory disorder. Physical activity (PA) may have a more important role in cardiovascular health than previously expected. This review overviews the contribution of PA to cardiovascular health, the inflammatory role of atherosclerosis, and the emerging evidence of the microbiome as a regulator of inflammation.

BACKGROUND:The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. METHODS:We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. CONCLUSION/CONCLUSIONS:The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span.

OBJECTIVE:The objective of the study is to investigate in the hypertensive population the possible differential association between increased aortic and/or carotid stiffness and organ damage in multiple districts, such as the kidney, the vessels, and the heart. METHODS:In 314 essential hypertensive patients, carotid-femoral pulse wave velocity (cfPWV, by applanation tonometry) and carotid stiffness (from ultrasound images analysis), together with left ventricular hypertrophy, carotid intima-media thickness, urinary albumin-creatinin ratio, and glomerular filtration rate were measured. Increased cfPWV and carotid stiffness were defined according to either international reference values or the 90th percentile of a local control group (110 age and sex-matched healthy individuals). RESULTS:When considering the 90th percentile of a local control group, increased cfPWV was associated with reduced glomerular filtration rate, either when carotid stiffness was increased [odds ratio (OR) 13.27 (confidence limits (CL) 95% 3.86-45.58)] or not [OR 7.39 (CL95% 2.25-24.28)], whereas increased carotid stiffness was associated with left ventricular hypertrophy, either when cfPWV was increased [OR 2.86 (CL95% 1.15-7.09)] or not [OR 2.81 (CL95% 1.13-6.97)]. No association between increased cfPWV or carotid stiffness and target organ damage was found when cutoffs obtained by international reference values were used. The concomitance of both increased cfPWV and carotid stiffness did not have an additive effect on organ damage. CONCLUSION:Aortic and carotid stiffness are differentially associated with target organ damage in hypertensive patients. Regional arterial stiffness as assessed by cfPWV is associated with renal organ damage and local carotid stiffness with cardiac organ damage.