| Autor: |
Nguyen LP; Department of Medicine and., Song W; Department of Medicine and., Yang Y; Department of Medicine and.; Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, USA., Tran AP; Department of Medicine and., Weston TA; Department of Medicine and., Jung H; Department of Medicine and., Tu Y; Department of Medicine and., Kim PH; Department of Medicine and., Kim JR; Department of Medicine and., Xie K; Department of Medicine and., Yu RG; Department of Medicine and., Scheithauer J; Department of Medicine and., Presnell AM; Department of Medicine and., Ploug M; Finsen Laboratory, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.; Finsen Laboratory, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark., Birrane G; Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Arnold H; Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden., Koltowska K; Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.; Beijer Gene and Neuro Laboratory, Uppsala University, Uppsala, Sweden., Mäe MA; Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden., Betsholtz C; Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.; Department of Medicine-Huddinge, Karolinska Institute Campus Flemingsberg, Huddinge, Sweden., He L; Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden., Goodwin JL; Division of Laboratory Animal Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA., Beigneux AP; Department of Medicine and., Fong LG; Department of Medicine and., Young SG; Department of Medicine and.; Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, USA. |
| Abstrakt: |
Lipoprotein lipase (LPL) and multiple regulators of LPL activity (e.g., APOC2 and ANGPTL4) are present in all vertebrates, but GPIHBP1-the endothelial cell (EC) protein that captures LPL within the subendothelial spaces and transports it to its site of action in the capillary lumen-is present in mammals but in not chickens or other lower vertebrates. In mammals, GPIHBP1 deficiency causes severe hypertriglyceridemia, but chickens maintain low triglyceride levels despite the absence of GPIHBP1. To understand intravascular lipolysis in lower vertebrates, we examined LPL expression in mouse and chicken hearts. In both species, LPL was abundant on capillaries, but the distribution of Lpl transcripts was strikingly different. In mouse hearts, Lpl transcripts were extremely abundant in cardiomyocytes but were barely detectable in capillary ECs. In chicken hearts, Lpl transcripts were absent in cardiomyocytes but abundant in capillary ECs. In zebrafish hearts, lpl transcripts were also in capillary ECs but not cardiomyocytes. In both mouse and chicken hearts, LPL was present, as judged by immunogold electron microscopy, in the glycocalyx of capillary ECs. Thus, mammals produce LPL in cardiomyocytes and rely on GPIHBP1 to transport the LPL into capillaries, whereas lower vertebrates produce LPL directly in capillary ECs, rendering an LPL transporter unnecessary. |
