Proteoglycans have been shown to play a critical role in the initiation of atherosclerosis due to their ability
to bind atherogenic lipoproteins leading to retention in the artery wall, as outlined in the “response to retention
hypothesis”. Research in Dr. Tannock's laboratory aims to identify the role of proteoglycans in the pathogenesis
of complications of diabetes and obesity, including atherosclerosis and nephropathy. Current studies are using
angiotensin II to regulate vascular proteoglycans in animal models of diabetes, obesity, and atherosclerosis.
Related studies are examining the interaction between inflammatory mediators/ markers and vascular proteoglycans.
Subjects with obesity, metabolic syndrome or diabetes have modest but chronic elevations in levels of the acute
phase reactants C reactive protein (CRP) and serum amyloid A (SAA). Dr Tannock has recently demonstrated that SAA
alters vascular proteoglycan synthesis in a pro-atherogenic manner, suggesting that the modest chronically elevated
levels of SAA seen in obese individuals could mechanistically contribute to atherosclerosis development. In
addition, recent research demonstrates that hyperlipidemia can adversely contribute to the development of diabetic
nephropathy, a process that may be mediated via renal accumulation of lipoproteins. The role of renal proteoglycans
in the development of diabetic nephropathy is another topic of investigation. A major focus of the lab is to identify
the underlying mechanisms that regulate proteoglycan synthesis and subsequently influence proteoglycan-lipoprotein
interactions. Results from these studies will advance our understanding of the mechanisms of atherosclerosis, and
may identify novel therapeutic targets to decrease lipoprotein retention as a strategy to prevent complications of
diabetes and obesity.