Claudia Stefanutti1, Fabio Mazza2, Daniela Pasqualetti3, Serafina Di Giacomo2, Gerald F Watts4, Maria Simona Massari3, Joel de Neve5, Claudia Morozzi2, Moritz Fischer6. 1. Extracorporeal Therapeutic Techniques Unit, Lipid Clinic and Atherosclerosis Prevention Centre, Department of Molecular Medicine, 'Sapienza' University of Rome, Rome, Italy. Electronic address: claudia.stefanutti@uniroma1.it. 2. Extracorporeal Therapeutic Techniques Unit, Lipid Clinic and Atherosclerosis Prevention Centre, Department of Molecular Medicine, 'Sapienza' University of Rome, Rome, Italy. 3. Integrated Laboratory for Cytometry and Quality, Department of Biotechnology and Haematology, 'Sapienza' University of Rome, Rome, Italy. 4. Cardiovascular Medicine, School of Medicine and Pharmacy, University of Western Australia, Perth, Western Australia, Australia. 5. LabOmics, Nivelles, Belgium. 6. Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
Abstract
BACKGROUND AND AIMS: Dyslipidaemias are associated with cardiovascular mortality and morbidity, driven by unstable atherosclerotic plaques with inflammatory infiltrates. Levels of messenger RNA (mRNA) for pro-inflammatory cytokines have been positively correlated with atherosclerotic disease progression. Therapeutic lipoprotein apheresis (LA) reduces plasma lipid levels and reduces inflammation. We evaluated the effects of LA on expression of mRNA coding for key pro-inflammatory cytokines in patients with dyslipidaemia, homo-/hetero-zygous familial hypercholesterolaemia (HoFH, HeFH) or hyperlipoprotein(a)aemia [hyperLp(a)] and associated coronary artery disease (CAD). APPROACH: Ten patients (five males and five females, mean age 47 ± 9.2 years) were enrolled, all with HyperLp(a) or confirmed genetic diagnoses of dyslipidaemia, HoFH, or HeFH; all had associated CAD. mRNA determinations were via reverse transcriptase polymer chain reaction (RT-qPCR). RESULTS: LA was associated with downregulation of mRNA expression for IL-1α, IL-6 and TNF-α, starting after the first LA session. The observed reduction was progressively enhanced during the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session (IL-1α: -49%, p < 0.001; IL-6: -35%, p < 0.001; TNF-α: -56%, p < 0.001). CONCLUSIONS: LA suppresses the expression of IL-1α, IL-6 and TNF-α mRNA in patients with dyslipidaemias. This may contribute to the arterial anti-inflammatory effect of LA.
BACKGROUND AND AIMS: Dyslipidaemias are associated with cardiovascular mortality and morbidity, driven by unstable atherosclerotic plaques with inflammatory infiltrates. Levels of messenger RNA (mRNA) for pro-inflammatory cytokines have been positively correlated with atherosclerotic disease progression. Therapeutic lipoprotein apheresis (LA) reduces plasma lipid levels and reduces inflammation. We evaluated the effects of LA on expression of mRNA coding for key pro-inflammatory cytokines in patients with dyslipidaemia, homo-/hetero-zygous familial hypercholesterolaemia (HoFH, HeFH) or hyperlipoprotein(a)aemia [hyperLp(a)] and associated coronary artery disease (CAD). APPROACH: Ten patients (five males and five females, mean age 47 ± 9.2 years) were enrolled, all with HyperLp(a) or confirmed genetic diagnoses of dyslipidaemia, HoFH, or HeFH; all had associated CAD. mRNA determinations were via reverse transcriptase polymer chain reaction (RT-qPCR). RESULTS: LA was associated with downregulation of mRNA expression for IL-1α, IL-6 and TNF-α, starting after the first LA session. The observed reduction was progressively enhanced during the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session (IL-1α: -49%, p < 0.001; IL-6: -35%, p < 0.001; TNF-α: -56%, p < 0.001). CONCLUSIONS: LA suppresses the expression of IL-1α, IL-6 and TNF-α mRNA in patients with dyslipidaemias. This may contribute to the arterial anti-inflammatory effect of LA.