title: Lipid loading of human vascular smooth muscle cells induces changes in tropoelastin protein levels and physical structure.
abstract: Aggregated low-density lipoprotein (agLDL), one of the main LDL modifications in the arterial intima, contributes to massive intracellular cholesteryl ester (CE) accumulation in human vascular smooth muscle cells (VSMC), which are major producers of elastin in the vascular wall. Our aim was to analyze the levels, physical structure, and molecular mobility of tropoelastin produced by agLDL-loaded human VSMC (agLDL-VSMC) versus that produced by control VSMC. Western blot analysis demonstrated that agLDL reduced VSMC-tropoelastin protein levels by increasing its degradation rate. Moreover, our results demonstrated increased levels of precursor and mature forms of cathepsin S in agLDL-VSMC. Fourier transform infrared analysis revealed modifications in the secondary structures of tropoelastin produced by lipid-loaded VSMCs. Thermal and dielectric analyses showed that agLDL-VSMC tropoelastin has decreased glass transition temperatures and distinct chain dynamics that, in addition to a loss of thermal stability, lead to strong changes in its mechanical properties. In conclusion, agLDL lipid loading of human vascular cells leads to an increase in cathepsin S production concomitantly with a decrease in cellular tropoelastin protein levels and dramatic changes in secreted tropoelastin physical structure. Therefore, VSMC-lipid loading likely determines alterations in the mechanical properties of the vascular wall and plays a crucial role in elastin loss during atherosclerosis.
authors.affiliation: Physique des Polymères, Institut Carnot, CIRIMAT UMR 5085, Université Paul Sabatier, Tolouse, France. Electronic address: valerie.samouillan@univ-tlse3.fr.
authors.forename: Valerie
authors.initials: V
authors.lastname: Samouillan
authors.affiliation: Physique des Polymères, Institut Carnot, CIRIMAT UMR 5085, Université Paul Sabatier, Tolouse, France.
authors.forename: Jany
authors.initials: J
authors.lastname: Dandurand
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Nasarre
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
authors.affiliation: Physique des Polymères, Institut Carnot, CIRIMAT UMR 5085, Université Paul Sabatier, Tolouse, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Lacabanne
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: cllorente@csic-iccc.org.
authors.forename: Vicenta
authors.initials: V
authors.lastname: Llorente-Cortés
mesh_terms: D000328:Adult; D001696:Biomechanical Phenomena; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D014333:Tropoelastin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D014333:Tropoelastin