Atherosclerosis

Dr. Yoshiyuki Yasuda, Dr. Andriy Samokhin, Dr. Martin Linke 

 

 Atherosclerosis (the hardening of arterial blood vessels) is the leading cause of death in North America. Fatty streak formation, blood vessel wall erosion, and plaque formation are hallmarks of the disease. Cathepsins have been implicated in all three steps of atherosclerosis. The scheme below summarizes these pathologies.

 

To investigate the role of cathepsins in atherosclerosis we use a disease mouse mouse model (ApoE-deficient mice) and various cathepsin-deficient mice strains.  Mice are studied for their expression levels of cathepsins, their elastin and collagen turnover in blood vessels, fatty streak and plaque formation as well as their rupture and on their reaction to cathepsin inhibitors. 

 

 

Staining of elastin fibrils in the tunica media revealed an increasing loss of those fibrils in areas of plaque formation. The macroscopic loss of elastin fibrils correlates with the significant increase of the elastin degradation marker, desmosine, in the serum of apoE-/- mice on high fat diet.

 

 
ApoE
-/- mice accumulate increasing amounts of lipids during the progression of the disease (red staining in the aortic arch).  Dissected aortas reveal massive occurrences of lipid-rich plaques after 16 weeks of high fat diet.