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Molecular Mechanisms of Adipose Tissue Survival during Severe Hypoxia: Implications for Autologous Fat Graft Performance
Sheri Wang, BS; Jeffrey A Gusenoff, MD; J Peter Rubin, MD, FACS; Lauren Kokai, PhD.
University of Pittsburgh
2019-02-15
Presenter: Sheri Wang
Affidavit:
I agree
Director Name: JP Rubin
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
BACKGROUND: Variable retention outcomes remain a significant issue in autologous fat grafting procedures. Amongst seemingly similar patients, using identical harvesting procedures, variability in graft retention is noted. Recent data suggests that the inherent characteristics of donor adipose tissue dictate graft healing outcomes. The goal of this study was to elucidate intrinsic qualities of human adipose tissue that confer resistance to ischemic stress to therapeutically target such mechanisms and improve overall results of fat grafts.
METHODS: Whole fat from 5 female patients was cultured in vitro under severe (1% O2) and mild (8% O2) hypoxic conditions. Microarray analysis of 44 hypoxia-related genes was performed. Perilipin was used to visualize viable adipocytes. Macrophage phenotypes were identified using PCR.
RESULTS: Analysis of adipocyte survival with perilipin suggested improved viability for tissue obtained from high BMI donors. Microarray data revealed a significant positive correlation for induced expression of ANGPTL4, a survival gene, and subject BMI (p=0.0313) during hypoxic conditions while HIF1α and HIF2α genes were negatively correlated with donor BMI (p=0.0003, 0.0303). Interestingly, induced differentiation of pro-inflammatory M1 macrophages was negatively correlated with BMI under hypoxia (p=0.0177).
CONCLUSION: Adipose tissue from high BMI donors demonstrates greater resistance to hypoxia induced apoptosis associated with increased expression of ANGPTL4. This has implications for therapeutic interventions, such as ischemic preconditioning, that can be applied to optimize clinical adipose graft survival.
