Bu. Raess et al., REGULATION OF RABBIT ERYTHROCYTE CA2-PUMP SENSITIVITY TO CALMODULIN IN EXPERIMENTAL HYPERLIPIDEMIA(), Proceedings of the Society for Experimental Biology and Medicine, 209(4), 1995, pp. 410-417
Intracellular free calcium activity Is in part determined by a calmodu
lin-regulated plasma membrane Ca2+-pump. Since changes in Ca2+ permeab
ility have been implicated In atherosclerotic plaque formation, we ini
tiated a lipid hyperallmentation protocol during which we measured var
ious erythrocyte calcium flux parameters and early atheroma developmen
t. Adolescent New Zealand White rabbits were fed a diet with 0.5% chol
esterol and 2.5% lard over a 3-month period. Plasma cholesterol and tr
iacylglycerols increased an average 18.7- and 13.9-fold respectively,
while erythrocyte membrane cholesterol content decreased 18% and total
phospholipids by 54%. After 3 months of lipid hyperalimentation, 22%
of the aortic arch was covered with large, early-stage, raised atherom
a. Basal and calmodulin-activated (Ca2+ + Mg2+)-ATPase activities in e
rythrocyte membranes increased by 31% and 123%, respectively at 2 mont
hs, with a concomitant increase in calmodulin affinity (K-m) from 15.6
to 4.2 nM. These differences were transient on account of changes in
the control animals which exhibited a slowly developing sensitivity to
calmodulin during maturation. Basal Ca2+ transport and passive Ca2+ p
ermeability increased about 7-fold during the hyperlipidemic phase. Th
is suggests that overt hyperlipidemia, leading to atherosclerotic plaq
ue development, alters plasma membrane Ca2+ regulatory mechanisms incl
uding passive Ca2+ permeability. The changes in enzymatic function, me
mbrane composition, and Ca2+ permeability seen in this red cell model
system may be a reflection of early changes in cells that are directly
involved in the development of atherosclerotic plaques.