The gut peptide bombesin reduced heart attack damage in rats by activating the Keap1-Nrf2-HO-1 antioxidant defense pathway, providing evidence for a protective gut-heart axis.
Gut-heart protectionBombesin peptide released under vagus nerve control protects the heart from reperfusion injury through Keap1-Nrf2-HO-1 antioxidant activation
What the researchers found
Bombesin improved cardiac function, reduced infarct size, attenuated oxidative stress (increased SOD, GSH; decreased MDA), and reduced apoptosis through Keap1-Nrf2-HO-1 pathway activation. All protective effects were blocked by a bombesin receptor antagonist.
Why it matters
Reperfusion injury is a major problem in cardiac medicine — it worsens damage even after successful treatment of a heart attack. Discovering that a natural gut peptide activates the heart's antioxidant defenses could lead to new protective strategies during cardiac procedures.
The numbers in context
Bombesin activated the Keap1-Nrf2-HO-1 pathway and reduced MIRI in both isolated heart and whole-animal models.
How the study worked
Two rat IRI models: ex vivo Langendorff perfused hearts (30 min global ischemia + 120 min reperfusion) and in vivo coronary artery ligation (30 min + 120 min reperfusion) in Sprague-Dawley rats. Measured infarct size, LV function, oxidative stress markers, apoptosis (TUNEL), and Keap1/Nrf2/HO-1 expression.
Who was studied
Animal models of myocardial ischemia/reperfusion injury (ex vivo and in vivo)
What this study cannot tell us
Animal study in rats — human cardiac physiology and bombesin responses may differ. Clinical administration of bombesin during a heart attack would require rapid delivery and precise timing. Safety profile of exogenous bombesin in cardiac patients is completely unknown. Single study with no replication reported.
How to read the evidence
Preliminary evidence: well-designed animal study using two complementary IRI models with clear mechanistic pathway identification, but no human data.
When this study was published
Published in 2024 in the journal Peptides. Novel finding connecting gut peptide signaling to cardiac protection.
The bigger picture
The gut-heart axis is an emerging area of cardiovascular research. This study shows that bombesin — a peptide connecting the vagus nerve, gut, and heart — can protect against one of cardiology's most significant unsolved problems. Combined with the vagus nerve stimulation findings, it suggests that gut-derived peptides may be natural cardioprotective signals.
Questions still open
- Could bombesin or bombesin receptor agonists be administered during cardiac procedures to prevent reperfusion injury?
- Do humans with higher natural bombesin levels have better outcomes after heart attacks?
- Would vagus nerve stimulation provide cardioprotection in humans through bombesin release?
Common questions
What is bombesin and where does it come from?
What is ischemia/reperfusion injury?
Read the original research
Bombesin protects myocardium against ischemia/reperfusion injury via activation of the Keap1-Nrf2-HO-1 signaling pathway.
Peptides, 180, 171279
Citation
Zhang, Jinyi; Du, Yanhuan; Xiong, Zhenyu; Cheng, Hang; Du, Yi; Xiong, Yulian; Lv, Jianfeng; Huang, Wenquan; Qiu, Kuncheng; Zhang, Shizhong. (2024). Bombesin protects myocardium against ischemia/reperfusion injury via activation of the Keap1-Nrf2-HO-1 signaling pathway.. Peptides, 180, 171279. https://doi.org/10.1016/j.peptides.2024.171279