In vitro uptake of dicarboxylic porphyrins by human atheroma. Kinetic and analytical studies.
Human atheromatous aorta segments as well as presumably disease-free control aorta were obtained at autopsy. They were incubated with solutions of various purified dicarboxylic porphyrins including hematoporphyrin (HP) and hydroxyethylvinyldeuteroporphyrin (HVD), and with solutions of Photofrin. Selective labelling of the atheroma was shown by macroscopic and microscopic observations of the characteristic porphyrin fluorescence associated with the atheromatous plaques. The time dependence of the uptake, monitored by absorption spectrophotometry or by high performance liquid chromatography, was inferred from the disappearance of the porphyrins in the incubation medium. Significant binding was observed in the absence of albumin or serum proteins. The uptake of HP was less than that of the more hydrophobic compounds HVD or Photofrin when these porphyrins were used alone. The presence of albumin or serum drastically reduces atheroma labelling. Some competition between HP and HVD for binding sites is also seen. The present results do indicate that hydrophobic porphyrins have an intrinsic affinity for atheroma and that they can be taken up through passive processes. Taking into account previous data on animal models (Photochem. Photobiol. (1989), 731-737), it appears however that, in vivo, interactions with proteins and pharmacokinetics will primarily determine plaque labelling.
Delettre
E
E
Laboratoire de Biophysique, INSERM U. 201, CNRS U.A. 481, Muséum National d'Histoire Naturelle, Paris, France.
Brault
D
D
Bruneval
P
P
Vever-Bizet
C
C
Dellinger
M
M
Delgado
O
O
Camilleri
J P
JP
Gaux
J C
JC
Peronneau
P
P
D001011:Aorta / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D001692:Biological Transport; D003905:Deuteroporphyrins / Q000378:metabolism*; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*
D003905:Deuteroporphyrins; D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D017324:Hematoporphyrin Derivative; C049889:hydroxyethylvinyldeuteroporphyrin