Abnormal transcriptomic profile of epicardial adipose tissue of people living with HIV: results from the PIECVIH study

Background: Increased epicardial adipose tissue (EAT) volume has been associated with increased risk of coronary artery disease (CAD) in people living with HIV (PLWH). However, the underlying mechanisms remain unknown. We conducted the PIECVIH study to compare EAT properties between PLWH and HIV-negative patients undergoing coronary artery bypass graft (CABG). Methods: The PIECVIH study is a cross sectional prospective study performed in one center (Sorbonne University hospital group, Paris, France) enrolling 11 ART-controlled PLWH and 11 matched (age +/- 3 years and sex) HIV-negative patients requiring CABG. During surgery, EAT and thoracic subcutaneous fat samples were taken. Transcriptomic analyses were performed in samples in which mRNA extraction led to enough mRNA of excellent quality i.e., in 7 PLWH and 7 HIV-negative samples for thoracic subcutaneous fat and 9 PLWH and 8 HIV-negative samples for EAT. The expression of 30 genes, related to inflammation, immune activation, fibrosis and adipokines, was evaluated and related to the expression of the reference gene 18S. Results: The mean age of the cohort was 59.8 years old (100% male). The cardiovascular risk profile was quite similar between both groups including 66% smokers, 64% had hypercholesterolaemia, 36% hypertriglyceridaemia and 56% hypertension. However, HIV-negative subjects had a higher prevalence of diabetes than PLWH (73% versus 18%; P=0.002) whereas body mass index was lower in PLWH (23.2 versus 27.5 kg/m2; P=0.017). Regarding transcriptomic analysis, the level of expression of all the tested genes was not different between PLWH and HIV-negative subjects in subcutaneous fat. Conversely, in EAT, the relative expression of IL-6 and CCL2 was 3-5-fold higher in samples issued from PLWH than from HIV-negative: respectively 0.46 versus 0.13 (P=0.03) and 1.13 versus 0.24 (P=0.03). Moreover, only in EAT and only in PLWH, the expression of CCL2 was highly related to the expression of collagen genes: COL6A3 (R=0.807, P=0.009), COL1A1 (R=0.726, P=0.027), COL6A2 (R=0.810, P