The Role of Cardiotrophin-Like Cytokine Factor 1 on the Development of Atherosclerosis
Metabolic syndrome represents a major global health problem. Its rate is constantly increasing. Cardiovascular diseases emerging from dyslipidemia conditions are a worldwide leading cause of death and morbidity, despite extensive medical research and wide range of drugs targeting atherosclerosis, obesity, diabetes etc.  Recent findings suggest the existence and persistence of low-grade inflammation in pathogenesis atherosclerosis and obesity. The “symbiosis” between metabolic and immune system is substantial and any perturbation contribute to the development of altered metabolic conditions that ultimately culminate in such disorders as obesity and atherosclerosis. The overall goal of my Master internship was to characterise the effect of cardiotrophin-like cytokine factor 1 on development of atherosclerosis and validate a long half-life derivative of cardiotrophin-like cytokine factor 1 coupled with Fc fragment of immunolglobulin G. Cardiotrophin-like cytokine factor 1 is a cytokine of the immune system with immunoregulatory activity. Cardiotrophin-like cytokine factor 1 belongs to the interleukin 6 family of monomeric cytokines. Cardiotrophin-like cytokine factor 1 is efficiently secreted in the presence of cytokine receptor like factor 1, a soluble cytokine receptor. Cardiotrophin-like cytokine 1 possesses neurotrophic activities mediated through the receptor of ciliary neurotrophic factor. Cardiotrophin-like cytokine factor 1 is a high affinity ligand for sortilin. Genome-wide association studies indicated that plasma low-density lipoprotein cholesterol levels and cardiovascular disease are associated with single nucleotide polymorphisms variants regulating sortilin expression. It was observed that cardiotrophin-like cytokine factor 1 binds and activates transfectants co-expressing sortilin and receptor of leukemia inhibitory factor. Both receptors are expressed by myeloid cells and leukemia inhibitory factor is a potent inducer of anti-inflammatory M2 macrophage differentiation.  The overall objective was to investigate if the interaction of cardiotrophin-like cytokine factor 1 or cardiotrophin-like cytokine factor 1 coupled with Fc fragment of immunoglobulin G with atherosclerotic plaque macrophages will reduce the foam cell formation and development of plaque. Our work shows that cardiotrophin-like cytokine 1 expression in mice on LDLR-/- atherosclerosis model does not decrease the development of plaque. However, some results revealed a significant contribution of cardiotrophin-like cytokine factor 1 in gain of body mass without changes in food intake.
Cardiotrophin-like cytokine factor 1 Inflammation Macrophages Immune System Sortilin Metabolic Syndrome Atherosclerosis