RECIPROCAL CHANGES IN LEFT-VENTRICULAR COLLAGEN ALPHA(1)-CHAIN GENE-EXPRESSION BETWEEN TYPE-I AND TYPE-IV IN SPONTANEOUSLY DIABETIC RATS

The characteristic features of diabetic cardiomyopathy have been repor ted to be increased collagen formation associated with impairment of v entricular performance, based on experimental models of diabetes. The present study was therefore designed to clarify collagen gene expressi on in hearts obtained from female spontaneously diabetic BioBreeding W orcester Tokyo (BB/W//Tky) rats. Cardiac hypertrophy was observed as e arly as 14 weeks in diabetic BB/W//Tky rats, i.e. 4 weeks after the on set of diabetes. Left ventricular gene expression of collagen alpha(1) (I) was decreased to 10.6% of the control level. In 24-week-old diabe tic rats, which had more marked cardiac hypertrophy, the level of alph a(1) Type I collagen mRNA was further decreased to 5.7% of the control level, whereas collagen alpha(1) (IV) mRNA demonstrated a 3-fold incr ease, As a result, a ratio of collagen alpha(1) (IV) to actin mRNA was positively correlated with plasma glucose concentration. These result s suggest that hyperglycemia may alter the gene expression of extracel lular matrix proteins, resulting in the morphological and functional c hanges seen in diabetic cardiomyopathy.