August 19, 2021

Potential protection from atherosclerosis

Vanderbilt researchers have discovered a potential way to reduce atherosclerosis: blocking the modification of an HDL-associated enzyme by reactive molecules called isolevuglandins.

PON1 (paraoxonase 1), an enzyme associated with high-density lipoprotein (HDL), breaks down lipid peroxides, highly reactive fatty molecules that can damage blood vessels.  

In this way, PON1 can protect against the development of cardiovascular disease. Numerous studies have observed reduced PON1 enzymatic activity in patients with cardiovascular disease. 

Reporting last month in the Journal of Biological ChemistrySean Davies, PhD, and colleagues demonstrate in vitro that other reactive molecules called isolevuglandins (IsoLGs) can directly modify PON1, and that direct modification is the primary mechanism by which IsoLG reduces PON1 activity. 

In collaboration with MacRae Linton, MD, and colleagues, the Davies group previously showed in a mouse model that scavenger molecules that bind to and remove IsoLGs from the bloodstream significantly enhanced PON1 activity. 

While further studies in vivo are necessary to determine the extent to which IsoLG modification of PON1 contributes to reduced enzyme activity, the current study supports the notion that blocking this modification could prove beneficial to reduce atherosclerosis, the researchers concluded.

The research was supported by National Institutes of Health grant HL116263.