Leptin mediates protective effects on the vasculature

Abstract Introduction and purpose Lipodystrophy (LD) syndromes are characterized by the loss of adipose tissue resulting in metabolic complications accelerated atherosclerosis. The systemic concentration adipokine leptin is reduced LD as a result deficiency. A therapeutical option to treat substitution leptin, which improves reduces mortality. However, vascular effects remain largely unknown. Here we analyze direct on system development Methods results Treatment human endothelial cells (ECs) with inflammation process endothelial-to-mesenchymal transition (EndMT) (CNN1, −41.4%, p<0.05, n=4). In addition, administration prevented EndMT-induced increase permeability. protective effect EndMT was confirmed vivo combined lipodystrophic atherosclerosis-prone mouse model (LDLR−/−; aP2-nSrebp1c). mice (3.0 mg/kg body weight daily for 8 weeks) decreased EndMT. Leptin showed no plaques size but protrusion atherosclerotic areas aortic roots (−31%, n=4–6). Cytokine screening revealed an growth differentiation factor 15 (GDF15) serum patients (+26.2%, n=53–58) ECs after (+138%, n=6743–10920). This reversed using treatment undergoing EndMT, model, 4 weeks administration. Indeed, GDF15 induced +7.7-fold-control, n=3), impaired EC barrier function. Neutralizing antibodies targeting inhibited EndMT-mediated expression mesenchymal genes −54%, from marker additional neutralizing −28%, n=3). Conclusion Our findings indicate that part cardiovascular disease progression lipodystrophy syndromes. has preventing inflammation, maintaining integrity. Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): Funded Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)