Expression and secretion of human apolipoprotein A-I in the heart.

Abstract

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.

• Authors: Nadine Baroukh, Camilo E Lopez, Maria Carla Saleh, Delia Recalde, Laurent Vergnes, Maria A Ostos, Laurence Fiette, Jean-Charles Fruchart, Graciela Castro, Mario M Zakin, Alberto Ochoa
• Journal: FEBS letters (FEBS Lett) Vol. 557 Issue 1-3 Pg. 39-44 (Jan 16 2004) ISSN: 0014-5793 [Print] England
• PMID: 14741338 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein A-I
• DNA Primers
• RNA, Messenger

Topics

• Animals
• Apolipoprotein A-I (genetics, metabolism)
• Base Sequence
• DNA Primers
• Gene Expression Regulation, Enzymologic
• Heart (metabolism)
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Myocardium (metabolism)
• Polymerase Chain Reaction
• RNA, Messenger (genetics)