Abstract: FR-PO191

Lipoprotein-Apheresis (LA) Slows Down Artery Disease Progression by Modulating the Cytokine Network Involved in the Atherosclerosis Signaling

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Simone, Simona, University of Bari, BARI, BARI, Italy
  • Accetturo, Matteo, University of Bari, BARI, BARI, Italy
  • Pontrelli, Paola, University of Bari, BARI, BARI, Italy
  • Zaza, Gianluigi, University of Verona, Verona, Italy
  • Rascio, F., University of Bari, BARI, BARI, Italy
  • Gesualdo, Loreto, University of Bari, BARI, BARI, Italy
  • Grandaliano, Giuseppe, UNIVERSITY OF FOGGIA, FOGGIA, Italy
  • Pertosa, Giovanni B., University of Bari, BARI, BARI, Italy
Background

LA is a potentially valuable treatment applied to conventional therapy-resistant patients with familial hypercholesterolemia (FH). Several clinical studies report that LA is associated with a significantly greater reduction of cardiovascular events, but the molecular mechanisms underlying this effect are still unknown.

Methods

Aim of the study was to evaluate the progression of atherosclerosis lesions (by measuring intima-media thickness, IMT, and the brachial artery Flow-Mediated Dilation, FMD) in 8 pts treated with LA (HELP system, BBraun, Italy). Moreover, by using a high-throughput approach, was also evaluated the transcriptomic profile in PBMCs isolated before and after LA (Agilent Technologies). The results were evaluated by statistical (Genespring software) and functional pathway analysis (Ingenuity Pathway Analysis, IPA). The data were validated by real-time PCR and ELISA test in an independent testing-group (n=10).

Results

A significant reduction of IMT (p<.001) was observed after 36 months of LA along with an increase of FMD (p<.02). Using a fold-change (FC) ≥2, we demonstrated that LA modulates the expression of 84 genes. The top canonical pathways was atherosclerosis signaling (p=.0003). Many pro-inflammatory cytokines involved in the development and progression of the atherosclerotic process were significantly down-regulated: Interleukin 1 (IL-1b FC=-2.97), IL-6 (FC=-2.07), IL-8 (FC=-3.56) and MCP-1 (FC=-2.13). Real Time PCR showed a different gene expression before and after LA (IL-1 p<.0004; IL-6: .01; IL-8 p<.005; MCP1 p<.0002). Similarly, circulating protein level (ELISA) confirmed that IL-1β (Pre 2.77±0.4pg/ml, After 0.93±0.2, p=0.003), IL-6 (Pre 2.09±0.6, After: 1.02 ±0.5 pg/ml, p=0.01), IL-8 (Pre 141.53±45.0, After: 27.9±5.2 pg/ml, p=0.008) and MCP1 (Pre 485.5±38.0, After 330.2±51.0 pg/ml, p=.0001) were down-regulated after LA.

Conclusion

Our data suggest that LA may contribute to cardiovascular risk reduction through the modulation of different pathways involved in the progression of atherosclerotic disease and improvement of microcirculation. This observation might open new perspectives in the prevention of cardiovascular risk in patients with FH

Funding

  • Government Support - Non-U.S.