The body Clock & Heart Attacks: Why Time of Day Matters & How New Research Could Save Lives
(Last Updated: October 26, 2023)
For decades, doctors have observed a troubling pattern: heart attacks occurring in the morning are significantly more dangerous than those happening later in the day. now, groundbreaking research from UTHealth Houston, published in the prestigious journal Nature, has finaly unlocked the molecular mechanisms behind this phenomenon, opening the door to potentially life-saving, time-targeted therapies. This isn’t just about when a heart attack happens; it’s about how our internal body clock – the circadian rhythm – dramatically influences the heart’s ability to survive and recover.
The Long-Observed Mystery: Why Morning Heart Attacks Are More Deadly
The link between time of day and heart attack severity isn’t new. Studies have consistently shown that individuals experiencing an acute myocardial infarction (heart attack) in the morning face a higher risk of fatal arrhythmias (irregular heartbeats), heart failure, and ultimately, death. but until now, the “why” remained elusive.
“If you have a heart attack in the morning, you are more likely to have fatal arrhythmias, heart failure, and you’re more likely to die from it,” explains Dr. Holger Eltzschig, MD, PhD, senior author of the study and Chair of the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston. “The question we asked is ‘Why?’ And we believe we’ve found a crucial piece of the puzzle.”
Unlocking the Molecular Code: BMAL1, HIF2A, and the Heart’s Response to Oxygen Deprivation
The UTHealth Houston team pinpointed a critical interaction between two proteins: BMAL1 and HIF2A. This revelation isn’t just incremental; it’s a essential shift in our understanding of how the heart responds to the stress of a heart attack. BMAL1 (Brain and Muscle ARNT-Like 1): Often referred to as a “master clock” protein,BMAL1 is central to regulating our circadian rhythm. It influences a vast array of biological processes, including sleep-wake cycles, metabolism, hormone release, and even immune function. Think of it as the conductor of the body’s internal orchestra.
HIF2A (Hypoxia-Inducible Factor 2 Alpha): This protein is the body’s key responder to hypoxia – a lack of oxygen. When oxygen levels drop, HIF2A kicks into gear, stimulating the production of red blood cells, encouraging the growth of new blood vessels (angiogenesis), and bolstering cell survival in low-oxygen environments. It’s the heart’s emergency response team.During a heart attack, blood flow to the heart muscle is blocked, creating a severe oxygen shortage. Researchers discovered that the interplay between BMAL1 and HIF2A dictates how heart cells respond to this oxygen deprivation. Crucially, this response isn’t constant; it fluctuates dramatically depending on the time of day.
The 3 AM vs. 3 PM Difference: A Dramatic Illustration
Preclinical studies using mice revealed a stark contrast. Heart attacks occurring around 3 a.m. resulted in significantly greater damage – larger infarct size (the area of dead heart tissue) and a heightened risk of heart failure. In contrast, heart attacks at 3 p.m. were less severe, with the heart demonstrating a superior ability to adapt to low oxygen levels and initiate efficient healing.
This difference isn’t random. It’s directly linked to the cyclical activity of BMAL1 and HIF2A.At 3 a.m., BMAL1 activity is at its lowest ebb, hindering HIF2A’s ability to effectively protect the heart. At 3 p.m., BMAL1 is more active, amplifying HIF2A’s protective mechanisms.
The AREG Gene: A Key Mediator of Time-Dependent Damage
further investigation revealed that BMAL1 and HIF2A work together to regulate a specific gene called amphiregulin (AREG). AREG plays a critical role in modulating the extent of heart damage throughout the day.By influencing AREG expression, these proteins essentially control the heart’s vulnerability to injury.
Targeting the Pathway: A New Era of Time-Sensitive Heart Attack Treatment?
The most exciting aspect of this research lies in its therapeutic implications. By targeting the BMAL1-HIF2A-AREG pathway with drugs,researchers were able to provide significant protection to the heart,especially when treatments were timed to coincide with the body’s natural circadian phase.
