Scientists link chronic methamphetamine abuse to cardiovascular disease risk

A study of mice conducted by Scripps research investigators has determined a link between chronic methamphetamine abuse and the risk of developing cardiovascular disease.

Washington, June 26 : A study of mice conducted by Scripps research investigators has determined a link between chronic methamphetamine abuse and the risk of developing cardiovascular disease.

Published in the Proceedings of the National Academy of Sciences, their study shows that long-term methamphetamine use causes aberrant by changing endogenous proteins in drug users. This raises the levels of pro-inflammatory cytokines, proteins involved in immune response.

The researchers believe that the increase in the levels of pro-inflammatory cytokines may be a previously unrecognised molecular mechanism for the development of cardiovascular disorders such as vasculitus, an inflammation of the blood vessels.

"Our previous studies showed that methamphetamine can glycate or add sugars to proteins," said Scripps Research Professor Kim Janda, who conducted this study in collaboration with Scripps Research Assistant Professor Tobin Dickerson and other colleagues.

"In this study, we found that the immune system responds dramatically to this methamphetamine-induced glycation, which may lead to vascular inflammation and deterioration if left untreated. These problems are the direct result of long-term methamphetamine abuse," said the researcher.

Janda said that previous studies might have missed the impact of chronic methamphetamine use on the vascular periphery, as they focused on the response of the microglia-the immune cells of the central nervous system-and the appearance of methamphetamine-related neurotoxicity in the central nervous system.

The study found that there was a direct relationship between methamphetamine intake and the level of circulating antibodies in animal models. Coupled with antibodies binding to methamphetamine, said Janda, such immune response might make the drug less biologically available, leading to an increased need for higher and higher doses.

Janda said if long-lived, the resulting glycated proteins-called advanced glycation endproducts (AGEs), which are associated with a number of diseases including diabetes and Alzheimer's disease, can easily modify protein function, initiate adverse cellular reactions, and form damaging deposits on arterial walls.

The study showed that Methamphetamine-AGE proteins not only increased antibody production, but were strong enough to overcome the drug's natural immunosuppressive qualities also.

It also showed that even limited daily access to the drug was enough to produce an over-expression of vascular endothelial growth factor (VEGF), a potent signaling cytokine involved in angiogenesis and vasodilation.

"Our data suggest that even methamphetamine use at lower doses may be enough to increase VEGF to potentially detrimental levels," Janda said.

ANI