(687.17) Soluble Isoform of ST2 is a Cardiac Inducer of Collagen Deposition in an Ex Vivo Model of Obesity

Poster Board Number: D41

Massimilano Corsi Romanelli (Department of Biomedical Sciences of Health,University of Milan, U.O.C. SMEL-1 Clinical Pathology IRCCS Policlinico San Donato), Chiara Copes (Department of Biomedical Sciences of Health,University of Milan), Elena Dozio (Department of Biomedical Sciences of Health,University of Milan), Clementina Sitzia (Department of Biomedical Sciences of Health,University of Milan), Emanuela Galliera (Department of Biomedical Sciences of Health,University of Milan, IRCCS Orthopedic Institute Galeazzi), Elena Vianello (Department of Biomedical Sciences of Health,University of Milan)

Introduction: One of the main cardiac mechanosensor is the IL-33/ST2L complex composed by the allarmin IL-33 released into extracellular space by damaged cells during cardiac overload and its receptor, ST2L, which their binding promotes cell survival and anti-fibrotic signaling. After damage, to stop IL-33/ST2L signal, resident cardiac cells release sST2, the soluble isoform of transmembrane receptor of ST2, which sequesters IL-33, functioning as a decoy receptor and blocking its signal. In obesity, the sST2 become over express especially by hypertrophic fat cells. The aim of our study is to evaluate in an ex vivo model of obesity the role of sST2 in the promotion of collagen production by cardiac cells.

Methods: Ten obese nondiabetic male Zucker rats (OB) (fa/fa-, 10 weeks of age) and 10 lean littermates (L) (Fa/+) at the age of 25 weeks were weighted and scarified according to Italian Ministry of Health Authorization (N°325/2015PR of 2015/04/05) and their heart and visceral adipose tissue (VAT) were collected for the analysis. VAT biopsies were cut in 30mg pieces and added into a co-culture system with H9C2 for 6-24 and 48 hours. At each time points, cells and culture medium were collected. In all samples were evaluated ST2 by ELISA and collagen were quantified by quantitative Sircol assay for measurement of both acid-soluble and pepsin-soluble collagens.

Results: OB cardiac biopsies showed higher protein level of both ST2 and collagen than L rats (plt;0.02 and plt;0.002 respectively) and the rat weight positively correlates with ST2 cardiac protein level (plt;0.05). Co-culture data demonstrated that OB VAT promotes ST2 releases in both cardiac and fat cells, resulting an incremental increase of sST2 release in cell culture medium than L VAT in time. sST2 quantification in correspondent H9C2 co-cultured lysate is more incremented in OB than L H9C2 after 48h.total collagen quantification in co-culture medium resulted higher in OB than L (plt;0.05).

Conclusion: Our results demonstrated in a co-culture system that obesity promotes sST2 increase in the heart and this promotes collagen releases by cardiac cells, suggesting sST2 role in activation of pro-fibrotic signaling and detrimental heart remodeling.

Support or Funding Information

This work was supported by funds from the Italian Ministry of Health “Ricerca Corrente” IRCCS Policlinico San Donato, and internal funds of the Department of Biomedical Sciences for Health of the Università degli Studi di Milano.

lt;pgt;This work was supported by funds from the Italian Ministry of Health amp;ldquo;Ricerca Correnteamp;rdquo; IRCCS Policlinico San Donato, and internal funds of the Department of Biomedical Sciences for Health of the Universitamp;agrave; degli Studi di Milano.lt;/pgt;