Carnitine requirement of vascular endothelial and smooth muscle cells in imminent ischemia.
Vascular endothelial and -smooth muscle cells have been shown to use fatty acids as substrates for oxidative phosphorylation. Endothelial cells are more vulnerable to oxidative stress than muscle cells and are prone to loose carnitine early during hypoperfusion. This has been suggested by two observations. The first is that incubation of isolated endothelial cells in a low carnitine medium leads to oleate oxidation, dependent upon carnitine addition, whereas smooth muscle cells do not depend on carnitine addition during in vitro incubation, although aminocarnitine, a specific inner-membrane carnitine palmitoyltransferase inhibitor, inhibits fatty acid oxidation. The second observation is that rat hearts labeled in vivo with 14C-carnitine loose, as paced Langendorff heart, only 4% of their carnitine in 20 min perfusion, following 60 min global ischemia. The carnitine released had a much higher specific radioactivity than the carnitine that was not released. It indicates compartmentation of carnitine in heart. As earlier and presently discussed work shows endothelial vulnerability, it is to be expected that this cell type may become carnitine deficient during pacing and ischemia. Endothelial incompetence in flow regulation could be delayed by the presence of carnitine and fatty acids in pre-ischemia. It is speculated how activated fatty acids could protect endothelium.
Hülsmann
W C
WC
Thorax Centre, Erasmus University, Rotterdam, The Netherlands.
Dubelaar
M L
ML
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002331:Carnitine / Q000502:physiology*; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D043586:Methylmalonyl-CoA Decarboxylase; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D051381:Rats
D002332:Carnitine O-Acetyltransferase; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase; D002331:Carnitine