Expression and secretion of human apolipoprotein A-I in the heart.
Various studies have correlated apolipoprotein (apo) A-I, the major component high-density lipoprotein, with protection against development of cardiovascular disease. Although apoA-I expression has been previously detected in the liver and intestine, we have discovered that the human apoA-I gene is also expressed in the heart. Using transgenic (Tg) mice generated with the human apoA-I/C-III/A-IV gene cluster and Tg mice produced with just the 2.2 kb human apoA-I gene, we have detected significant levels of apoA-I expression in the heart. Furthermore, the detection of apoA-I expression in the hearts of human apoA-I Tg mice indicates that the minimal regulatory elements necessary for cardiac expression of the gene are located near its coding sequence. To determine if the apoA-I gene is also expressed in the human heart, similar analyses were performed, where apoA-I expression was found in both adult and fetal hearts. Furthermore in-depth investigation of the various regions of human and Tg mouse hearts revealed that the apoA-I mRNA was present in the ventricles and atria, but not in the aorta. In situ hybridization of Tg mouse hearts revealed that apoA-I expression was restricted to the cardiac myocyte cells. Finally, heart explants and cardiac primary culture experiments with Tg mice showed secretion of particles containing the human apoA-I protein, and metabolic labeling experiments have also detected a 28 kDa human apoA-I protein secreted from the heart. From these novel findings, new insights into the role and function of apoA-I can be extrapolated.
Baroukh
Nadine
N
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France. nnbaroukh@lbl.gov
Lopez
Camilo E
CE
Saleh
Maria Carla
MC
Recalde
Delia
D
Vergnes
Laurent
L
Ostos
Maria A
MA
Fiette
Laurence
L
Fruchart
Jean-Charles
JC
Castro
Graciela
G
Zakin
Mario M
MM
Ochoa
Alberto
A
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D016632:Apolipoprotein A-I; D017931:DNA Primers; D012333:RNA, Messenger