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Collagen VI Alpha-3 Expression Is Higher In The Superficial Epigastric Adipose Tissue Of Former Smokers Than In Non-smokers
George A. Taylor, MD1, Edwin Acevedo, Jr., MD1, David Dugue, BS2, Alexa Deemer, BS2, Andrew A. Gassman, MD3, Evangelia Bellas, PhD4.
1Department of Surgery, Temple University Hospital, Philadelphia, PA, USA, 2Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA, 3Department of Plastic and Reconstructive Surgery, Temple University Hospital, Philadelphia, PA, USA, 4Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USA.

PURPOSE: Collagen VI (Col6) is an extracellular matrix (ECM) protein that plays a role in adipose tissue architecture by providing a framework for cellular connections to the ECM. Its overexpression in adipose tissue is associated with metabolic derangements such as insulin resistance and tissue fibrosis. The alpha-3 subunit of Collagen VI (Col6a3) has specifically been implicated in insulin resistance and inflammatory pathways via a cleaved mediator known as endotrophin. While previous clinical literature has shown that former smokers have an increased risk of wound complications following major surgery (including surgical site infection, disruption, delayed healing, and hernia, among others), the molecular basis for this is unclear. Moreover, the Col6a3 subunit has not been studied in this setting. Our study sought to examine the expression of Col6a3 among adipose tissue collected from obese and overweight patients following massive weight loss, and to characterize differences among patients based on preoperative comorbidities.
METHODS: Patients undergoing abdominoplasty following massive weight loss were consented for tissue donation for laboratory examination. The abdominal tissue samples were sampled in three distinct anatomic locations, the epigastric, periumbilical and hypogastric regions. Samples were collected both deep and superficial to Scarpa’s fascia in each location. mRNA was extracted from each sample for RT-qPCR. Results of the qPCR assay were normalized locally to the reference gene beta-actin, and globally to the same periumbilical depot per patient. Gene expression levels were calculated using the 2-delta-delta fold-change method. Average gene expression levels were compared among different cohorts based on comorbidities.
RESULTS:
To date, eleven (11) patients have undergone abdominoplasty and were included in the study. All patients were female. Average BMI at the time of abdominoplasty was 30.98. There were five (5) former smokers, six (6) non-smokers, and zero (0) current smokers. Average time since cessation of smoking was 29 months prior to abdominoplasty, with an average of 13.8 pack-years smoked. There was significantly higher Col6a3 gene expression in the epigastric region superficial to Scarpa’s fascia among former smokers when compared to the same depot in non-smokers (2.1-fold higher expression than the reference depot versus 0.1-fold, p = 0.02). There was no difference in mean adipocyte size between former smokers and non-smokers in this depot (p=0.97).
CONCLUSION:
Col6a3 gene expression in the superficial epigastrium is higher among former smokers than in non-smokers. This finding suggests another possible role of Col6a3, as a mediator of tissue fibrosis in former smokers. This, along with its association with insulin resistance, may implicate Col6a3 as the molecular culprit in wound complications among obese patients who are former smokers. Long-term follow up of this cohort is warranted for evaluation of wound complications.


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