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Expression and secretion of human apolipoprotein A‐I in the heart
Author(s) -
Baroukh Nadine,
Lopez Camilo E,
Saleh Maria-Carla,
Recalde Delia,
Vergnes Laurent,
Ostos Maria A,
Fiette Laurence,
Fruchart Jean-Charles,
Castro Graciela,
Zakin Mario M,
Ochoa Alberto
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01429-7
Subject(s) - apolipoprotein b , gene expression , biology , medicine , endocrinology , genetically modified mouse , in situ hybridization , transgene , secretion , gene , lipoprotein , human heart , microbiology and biotechnology , cholesterol , biochemistry
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.