Harnessing the heart's natural defense against heart attack damage

Researchers are exploring the potential of the body's natural response to low oxygen to mitigate heart damage during heart attacks and surgical procedures, utilizing currently available medications. Published in Nature Reviews Cardiology, a review authored by Holger Eltzschig and his team sheds light on proteins known as hypoxia-inducible factors (HIFs), which function as oxygen sensors in the body.

When oxygen levels plummet, such as during a heart attack, HIFs trigger a series of protective genes that aid cellular survival. These genes facilitate the heart's adaptation to low-oxygen conditions by altering energy production, diminishing cellular stress, and stimulating other protective mechanisms.

Myocardial infarction, or heart attack, is a leading cause of mortality in patients undergoing surgery. Eltzschig, a distinguished professor at McGovern Medical School at UTHealth Houston, has dedicated significant effort to discovering novel methods to safeguard heart muscle against oxygen deprivation-induced damage. A heart attack transpires when blood flow to the heart muscle is impeded or obstructed by partially or entirely blocked arteries, leading to oxygen deprivation that can result in cell death and inflammation.

Although restoring blood flow is crucial, the abrupt surge in oxygen can also inflict further harm, a phenomenon referred to as ischemia-reperfusion injury.

Eltzschig's previous research unveiled that the timing of a heart attack can impact the severity of heart damage, with this effect attributed to an interaction between BMAL1, a circadian rhythm protein, and HIF2A, a protein facilitating low-oxygen adaptation. These proteins modulate heart cell response post-heart attack, potentially influencing the extent of injury.

This discovery spurred the team to investigate whether activating HIF2A in the early morning could enhance protection against heart damage. The review delves into HIF proteins as pivotal regulators of the heart's response to low oxygen and posits that HIF-activating drugs could eventually be employed to shield the heart during heart attacks and surgery.

The review emphasizes two HIF proteins—HIF1A and HIF2A—that may contribute to heart protection via distinct mechanisms. HIF1A plays a critical role in ischemic preconditioning, wherein brief, controlled reductions in blood flow seemingly "train" the heart to better tolerate future heart attacks. HIF2A, on the other hand, may offer supplementary protection influenced by the body's inherent circadian rhythms.

In both animal and laboratory studies, medications that augment HIF activity have consistently diminished heart damage induced by heart attacks. Nevertheless, these interventions have yet to become standard practice for heart patients, although certain HIF-activating therapies are already authorized by the FDA for other ailments.

Researchers anticipate forthcoming clinical trials to ascertain whether HIF-activating drugs can diminish heart damage during acute heart attacks, safeguard the heart during major cardiac surgery, and forestall heart injury during other surgical operations.