Expression of mRNA for Matrix γ-Carboxyglutamic Acid Protein during Progression of Atherosclerosis in Aortae of Watanabe Heritable Hyperlipidemic Rabbits1

In an effort to characterize mRNAs that are highly expressed during atherosclerosis, we employed differential hybridization screening of a cDNA library constructed from total RNA derived from the aorta of Watanabe heritable hyperlipidemic (WHHL) rabbits. Characterizing the cDNAs for mRNAs that are present in large amounts in WHHL rabbit aortae, we identified a positive clone encoding matrix gamma-carboxyglutamic acid protein (MGP). The primary structure of rabbit MGP was deduced from nucleotide sequence analysis of the cDNA. Northern blot analysis of total RNA prepared from aortae of WHHL and normal rabbits of various ages indicated that the expression of MGP mRNA increased in proportion to the progression of atherosclerosis in WHHL rabbits. Analysis of MGP mRNA by in situ hybridization revealed that a significant amount of MGP mRNA is accumulated in atherosclerotic lesions of WHHL rabbits, suggesting that the expression of MGP mRNA is correlated with the progression of atherosclerosis.