Cholesterol homeostatic mechanisms in transgenic mice with altered expression of apoproteins A-I, A-II and A-IV.
Our understanding of the in vivo metabolic functions of apoA-I and A-II has greatly advanced with the use of transgenic mice, but the physiological role of apoA-IV remains elusive. Both apoA-I and A-II are necessary for the structural stability of high-density lipoprotein (HDL). Structural differences exist between human and mouse A apoproteins because: i) human cholesterol ester transfer protein, lecithin cholesterol acyl transferase and phospholipid transfer protein interact better with human apoA-I; ii) human apoA-I and A-II, alone or in combination, form polydisperse instead of monodisperse HDL particles. Human apoA-II overexpression has highlighted its inhibitory effect on lipoprotein lipase and hepatic lipase, resulting in hypertriglyceridemia and concomitantly decreased HDL and apoA-I. After long-term challenge with an atherogenic diet, mice are less protected against lesion formation by human apoA-II, mouse apoA-II being overtly proatherogenic. On the other hand, human apoA-I confers great protection against lesion formation and causes reduction of preexisting lesions. Human apoA-IV is also protective, although the mechanisms by which this protection is achieved remain to be determined.
Kalopissis
A D
AD
U505 INSERM, Centre de Recherche des Cordeliers, Paris, France. athina.kalopissis-u505@bhdc.jussieu.fr
Chambaz
J
J
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics; D016633:Apolipoprotein A-II / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D001054:Apolipoproteins A / Q000096:biosynthesis* / Q000235:genetics; D001161:Arteriosclerosis; D001693:Biological Transport, Active; D002784:Cholesterol / Q000378:metabolism*; D004198:Disease Susceptibility; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; C022205:apolipoprotein A-IV; D002784:Cholesterol