Analysis of atherosclerosis susceptibility in mice with genetic defects in platelet function.
To determine whether platelets contribute to the development of atherosclerosis, we compared the severity of atherosclerosis in susceptible C57BL/6 mice carrying either a normal or a variant phenotype for platelet function. Five genetically distinct mutants with increased bleeding times and abnormal dense granules were used: maroon (ru-2mr), light ear (le), ruby eye (ru), beige (bg1), and pale ear (ep). After a 14-week consumption of an atherogenic diet, three mutants had significantly less disease involvement than the control: light ear, maroon, and ruby eye. In contrast, pale ear ahd lesions similar to control animals. After 48 weeks, the two mutants with the least degree of atherosclerosis at 14 weeks, light ear and ruby eye, showed greater than 50% survival. In contrast, no animals from the beige, pale ear, or the normal C57BL/6 strains survived. To determine whether a specific biochemical component of platelet function is related to atherosclerosis, we measured serotonin found in dense granules. Serotonin showed no correlation with each mutant's atherosclerosis susceptibility. These results indicate that some particular component of platelet function affects atherosclerosis. That component is intact in pale ear, moderately affected in beige and maroon, and severely affected in light ear and ruby eye. The identity of that component remains an interesting question whose answer may provide further insight into the atherosclerotic disease process.
Paigen
B
B
Children's Hospital, Oakland Research Institute, Children's Hospital Medical Center, California.
Holmes
P A
PA
Novak
E K
EK
Swank
R T
RT
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D001792:Blood Platelets / Q000032:analysis / Q000502:physiology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL / Q000097:blood / Q000235:genetics*; D008817:Mice, Mutant Strains / Q000097:blood / Q000235:genetics*; D009154:Mutation; D012701:Serotonin / Q000032:analysis
D012701:Serotonin