Aims: Cardiac disease is a common complication in diabetes. Loss of NO bioviability and an induction of TGF-ß1 play a key role in the response of cardiomyocytes to hyperglycaemia. Using eNOS heterozygous mice that overexpress TGF-ß1 we observed recently an up-regulation of the proteogylcan biglycan in failing hearts. In order to identify a potential role of biglycan in cardiac remodelling we investigated the cardiac regulation of pro-fibrotic and pro-hypertrophic genes in normal and diabetic biglycan knockout mice (BGN-/-).

Methods: 

BGN-/- and their wild-type littermates were used as non-diabetic controls and in a diabetes model (strepotozotin). Hearts were removed, quickly frozen, the RNA was extracted and the mRNA expression was quantified by real time RT-PCR.

Results: 

Diabetes itself did not induce the cardiac expression of biglycan, but that of ANF and laminin. In BGN-/- mice no differences to the non-transgenic littermates were observed in the absence of diabetes. However, in diabatic knockout mice there was a significant up-regulation of elastin and decorin but no suppression of the diabetic induced ANF and laminin expression. Interestingly, a similar trend was found in the lung of eNOS heterozygous mice that developed a mild form of heart disease in which biglycan mRNA expression was reduced by 24% compared to wild type mice and elastin was increased by 44% (p=0.022).

Conclusion: 

Biglycan seems to be involved in the regulation of elastin and decorin keeping the mRNA expression of both genes in the normal range. As a similar increase of cardiac elastin to collagen-1 ratio was also found eNOS heterozygous mice where it directly correlates with the disease state of the mice. Therefore, we conclude that biglycan plays a protective role in diabetic hearts.