title: Dyslipidemia and Diabetes Increase the OPG/TRAIL Ratio in the Cardiovascular System.
abstract: Background. Dyslipidemia and diabetes are two of the most well established risk factors for the development of cardiovascular disease (CVD). Both of them usually activate a complex range of pathogenic pathways leading to organ damage. Here we hypothesized that dyslipidemia and diabetes could affect osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) expression in the vessels and the heart.Materials and Methods. Gene and protein expression of OPG, TRAIL, and OPG/TRAIL ratio were quantified in the aorta and the hearts of control mice, dyslipidemic mice, and diabetic mice.Results. Diabetes significantly increased OPG and the OPG/TRAIL ratio expression in the aorta, while dyslipidemia was the major determinant of the changes observed in the heart, where it significantly increased OPG and reduced TRAIL expression, thus increasing cardiac OPG/TRAIL ratio.Conclusions. This work shows that both dyslipidemia and diabetes affect OPG/TRAIL ratio in the cardiovascular system. This could contribute to the changes in circulating OPG/TRAIL which are observed in patients with diabetes and CVD. Most importantly, these changes could mediate/contribute to atherosclerosis development and cardiac remodeling.
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy.
authors.forename: Barbara
authors.identifier: 0000-0002-6854-5782
authors.initials: B
authors.lastname: Toffoli
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fabris
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bartelloni
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy.
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy.
authors.forename: Stella
authors.identifier: 0000-0002-7429-3075
authors.initials: S
authors.lastname: Bernardi
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000378:metabolism*; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053244:Osteoprotegerin / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D053244:Osteoprotegerin; D053221:TNF-Related Apoptosis-Inducing Ligand; C506031:Tnfrsf11b protein, mouse; C505654:Tnfsf10 protein, mouse