Investigating the platelet contribution to diet induced PVAT leukocyte infiltration

Abstract

Background: Perivascular adipose tissue (PVAT) is an adipocyte and leukocyte depot that encircles most peripheral arteries and aids in the regulation of vascular tone. Under normal physiological conditions PVAT mediates vascular relaxation, but under obesogenic conditions, such as those caused by poor nutrition, PVAT loses its anti-contractile properties, thus contributing to increased vascular tone. This change in PVAT phenotype is marked by the replacement of native anti-inflammatory leukocytes with pro-inflammatory counterparts which facilitate an inflamed, hypertensive phenotype. As platelets have been shown to aid in the infiltration of leukocytes into infected tissues from the circulation, we investigated whether platelets are significant contributors to the leukocyte recruitment that marks the PVAT phenotypic/functional shift resulting from poor nutrition. Methods: To determine the impact of platelets on the diet induced phenotypic shift in PVAT leukocyte composition, male C57BL6/J mice were administered a platelet depleting antibody or vehicle control for 2 weeks prior to the isolation of the thoracic and abdominal PVAT depots whereupon leukocyte composition was determined via flow cytometry. Dietary interventions included either a control (10% fat, 7% sucrose, 0.3% salt Research Diets Inc. D12450J) or Western (40% fat, 30% sucrose, 8% salt Research Diets Inc. D06111701) diet to either maintain PVAT or facilitate disruption. Two cohorts of mice were utilized with one fed diet for 8 weeks beginning at the time of weaning (4 weeks of age) and another for 2 weeks beginning at 10 weeks of age to elucidate whether platelets are an early or ongoing facilitator of PVAT perturbation. Results: Compared to control diet, Western diet shifted the lymphocyte content of the thoracic PVAT depot such that there was a higher proportion of CD4+ T cells; however, this was not observed in abdominal PVAT. With regards to the myeloid cell population, Western diet facilitated a reduction in thoracic PVAT nonclassical monocytes and macrophages while additionally increasing the proportion of classical monocytes in abdominal PVAT. Furthermore, a Western diet nominally reduced the proportion of proliferative macrophages in both thoracic and abdominal PVAT. Conclusions: A Western diet influences the composition of both the thoracic and abdominal PVAT depots by altering monocyte polarization, as well as influencing macrophage and T cell distribution within the tissue. This shift in leukocyte populations is congruent with an overall phenotypic switch towards a more pro-inflammatory and thus vasoconstrictive environment as previously noted to be driven by obesogenic dietary interventions. Funding: ACRI/ABI AWD-037176. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.