Abstract P159: Adipocyte Progenitor Subtypes In Perivascular Adipose Tissues: Effect Of Site And Spatial Location

Abstract

Hypertension-induced remodeling leads to excessive extracellular matrix (ECM) deposition in the different vascular tunicas including the outermost layer, perivascular adipose tissue (PVAT). Hypertension also reduces PVAT adipocyte populations. The number of adipocytes are maintained by continuous adipogenesis of progenitor cells (AP) expressing PDGFRα, but not all AP are created equal. In brown adipose tissue (AT), distinct AP subpopulations have defined spatial distributions and distinct adipogenic and fibrogenic potential. For example, Bmper + AP are restricted to brown AT parenchyma and express Col IV and V; these preferentially differentiate into adipocytes. Fibro-adipogenic AP such as Pi16 + abound in the fascia and express Fn1 and Col XII, while Gdf10 + close to blood vessels express Col I and Fbln1. However, how AP subtypes distribute in and contribute to PVAT remodeling is currently unknown. We hypothesize that AP subtypes from PVAT have different spatial distributions. We collected PVAT from the thoracic (atPVAT) and abdominal (abPVAT) aorta and mesenteric (mesPVAT) sites from 30-week-old male lineage tracing mice ( PDGFRa -CreERT2/R26-LSL-tdTomato; n = 5). We traced Pdgfrα + AP by inducing tdTomato expression (tamoxifen, 150 mg/kg, IP, 5d). Arterial sections with PVAT were stained (6-plex IHC) with DAPI and antibodies against BMPER, PI16, GDF10, and PPARG to define AP subpopulations in the fascia, parenchyma, and adventitia using ImageScope Cellular IF Algorithm (reported as % cells/total AP±SD). In all PVAT depots, we found the presence of all AP subtypes. BMPER and PPARG had a nuclear expression, while PI16 and GDF10 were in the cytoplasm and membrane. APs co-expressing PPARG were highly abundant in the parenchyma of atPVAT (82% 8 of 10±15.3) vs. mesPVAT (37% 4 of 11±22.1). BMPER and PI16 had no differences in their PVAT distribution. In atPVAT, GDF10 had higher expression in the adventitia (72% 8 of 11±24) vs. parenchyma (36% 4 of 11±23.2) and fascia (16% 3 of 18±15.2). Our results show the diversity of AP populations in different PVAT depots, which can contribute differently to hypertension-induced PVAT remodeling. Future experiments will evaluate how hypertensive conditions affect the fate of AP subtypes in PVAT.