Antioxidant pathway disruption may prevent heart disease

Researchers have found that deficiency of an antioxidant response protein called nuclear erythroid-2 like factor-2 (Nrf2) is capable of delaying or preventing hypertrophic cardiomyopathy, a type of a heart failure in which the heart muscle grows abnormally thick.

This new finding suggests that restoring the normal balance of reduction-oxidation chemical reactions in the body could prevent heart disease and other conditions caused by reductive stress.

Nuclear erythroid-2 like factor-2 (Nrf2) is a key regulatory protein in the signaling pathway that triggers the body's primary defense against oxidative stress, a condition where increased production of oxygen-containing free radicals causes cell damage.

Many cardiac diseases, including hypertrophic cardiomyopathy, are linked to oxidative stress.

Principal author Namakkal S. Rajasekaran, Ph.D., research assistant professor of internal medicine at the University of Utah, said that heart muscle cells, like all cells, are sensitive to shifts in the chemical reactions occurring inside and around them.

Rajasekaran and his team studied laboratory mice with heart disease caused by mutations in alpha B-Crystallin, a protein that normally helps other proteins fold inside cells.

These mice develop mutant protein aggregation cardiomyopathy (MPAC), a type of heart failure characterized by reductive stress and protein aggregation, the clumping together of misfolded proteins.

The researchers compared two strains of MPAC mice - one with normal Nrf2 and another with Nrf2 deficiency. They found that, while mice with normal Nrf2 developed heart muscle thickening and heart failure, mice that were deficient in Nrf2 did not.

The findings have been published in journal Cardiovascular Research.