Redox-regulated adaptive pathways in heart failure (renewal)

A chemical that damages heart muscle in one form may protect it in another—and researchers are now working out how to harness the protective version for treatment. Heart failure occurs when the heart cannot pump enough blood, often because chronic high blood pressure or other stresses have thickened and scarred the heart muscle. For years, scientists believed that all reactive oxygen species—highly reactive chemicals that can damage cells—were harmful in heart failure. But this team discovered that one particular enzyme, NOX4, actually helps the heart adapt to stress by triggering several protective pathways: it boosts blood vessel growth, activates cellular defence systems, and reprograms how heart cells use energy. Meanwhile, a related enzyme, NOX2, does the opposite—it drives the damage that leads to heart failure. If the researchers can work out exactly how NOX4 triggers these beneficial effects, they may identify new drug targets that mimic its protective actions without blocking the harmful NOX2. This could lead to treatments that help the heart cope with chronic stress, potentially slowing or preventing the progression of heart failure. The work also explains why previous attempts to treat heart failure with general antioxidants failed—they wiped out both the harmful and the helpful reactive oxygen species.