EnglishA soluble form of human low-density lipoprotein receptor (LDL-R) fused in frame with rabbit transferrin (LDL-Rs(hu)/Tf(rab)) is assessed in vivo as a therapeutic tool for lowering plasma LDL cholesterol. The cDNA encoding LDL-Rs(hu)/Tf(rab) is expressed in mice, using a hydrodynamics-based gene transfer procedure. The transgene is transcribed in the liver of transduced animals and the corresponding protein is secreted into the bloodstream. Circulating LDL-Rs(hu)/Tf(rab) binds LDL specifically, thus indicating that it is correctly processed through the cellular compartments in vivo. More importantly, the expression of LDL-Rs(hu)/Tf(rab) allows the removal of injected human (125)I-labeled LDL ((123)I-LDL) from the bloodstream of transduced CD1 mice, which show faster LDL plasma clearance, anticipating by approximately 90 min the same clearance value observed in control animals. A similar effect is observed in transduced LDL-R(-/-) mice, in which the clearance of injected human LDL depends solely on the presence of circulating LDL-Rs(hu) /Tf(rab). In these animals the extent of plasma LDL clearance is directly related to the concentration of LDL-Rs(hu)/Tf(rab) in the blood. Finally, LDL-Rs(hu)/Tf(rab) does not alter the pattern of LDL organ distribution: in transduced animals, as well as in control animals, liver and bladder are the predominantly labeled organs after (123)I-LDL injection. However, LDL-Rs(hu)/Tf(rab) has a quantitative effect on LDL tissue deposition: in treated animals LDL-Rs(hu)/Tf(rab) determines an increase in radioactivity in the liver at early times after (123)I-LDL injection and a progressive labeling of the bladder, starting 20 min after injection.
Low-density lipoprotein (LDL) receptor/transferrin fusion protein: in vivoproduction and functional evaluation as a potential therapeutic tool forlowering plasma LDL cholesterol / Razzini, Giorgia; Parise, Flavia; Calebiro, D; Battini, Renata; Bagni, Bruno; Corazzari, Tolmino; Tarugi, Patrizia Maria; Angelelli, Cecilia; Molinari, Susanna; Falqui, L; Ferrari, Stefano. - In: HUMAN GENE THERAPY. - ISSN 1043-0342. - STAMPA. - 15 (6)(2004), pp. 533-541.
| Data di pubblicazione: | 2004 |
| Titolo: | Low-density lipoprotein (LDL) receptor/transferrin fusion protein: in vivoproduction and functional evaluation as a potential therapeutic tool forlowering plasma LDL cholesterol. |
| Autore/i: | Razzini, Giorgia; Parise, Flavia; Calebiro, D; Battini, Renata; Bagni, Bruno; Corazzari, Tolmino; Tarugi, Patrizia Maria; Angelelli, Cecilia; Molinari, Susanna; Falqui, L; Ferrari, Stefano |
| Autore/i UNIMORE: | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1089/104303404323141980 |
| Rivista: | |
| Volume: | 15 (6) |
| Pagina iniziale: | 533 |
| Pagina finale: | 541 |
| Codice identificativo ISI: | WOS:000222258500001 |
| Codice identificativo Scopus: | 2-s2.0-14744292260 |
| Codice identificativo Pubmed: | 15212712 |
| Citazione: | Low-density lipoprotein (LDL) receptor/transferrin fusion protein: in vivoproduction and functional evaluation as a potential therapeutic tool forlowering plasma LDL cholesterol / Razzini, Giorgia; Parise, Flavia; Calebiro, D; Battini, Renata; Bagni, Bruno; Corazzari, Tolmino; Tarugi, Patrizia Maria; Angelelli, Cecilia; Molinari, Susanna; Falqui, L; Ferrari, Stefano. - In: HUMAN GENE THERAPY. - ISSN 1043-0342. - STAMPA. - 15 (6)(2004), pp. 533-541. |
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