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Both Ghrelin and Its Inactive Form Des-Acyl Ghrelin Protect Heart and Blood Vessel Cells From Death

RPEP-007122002Baldanzi, Gianluca; Filigheddu, Nicoletta; Cutrupi, Santina; Catapano, Filomena; Bonissoni, Sara; Fubini, Alberto; Malan, Daniela; Baj, Germano; Granata, Riccarda; Broglio, Fabio; Papotti, Mauro; Surico, Nicola; Bussolino, Federico; Isgaard, Jorgen; Deghenghi, Romano; Sinigaglia, Fabiola; Prat, Maria; Muccioli, Giampiero; Ghigo, Ezio; Graziani, Andrea
In VitroModerate evidence
The takeaway

Both acylated ghrelin and its des-acyl form (which doesn't activate the classical GHS receptor) protected cardiomyocytes and endothelial cells from apoptosis through ERK1/2 and PI3K/Akt survival pathways — a GHS-R independent mechanism.

Inactive form active!

Des-acyl ghrelin — previously considered inactive — protects heart cells through its own receptor, separate from the classical ghrelin receptor

What the researchers found

Both acylated ghrelin and des-acyl ghrelin inhibited apoptosis in cardiomyocytes and endothelial cells via ERK1/2 and PI3K/Akt pathways, with des-acyl ghrelin's activity demonstrating GHS-R-independent cardiovascular protection.

Why it matters

Des-acyl ghrelin is the most abundant form in blood. If it protects the heart independently of the GHS receptor, it represents a major, previously unrecognized cardiovascular protective system with its own unknown receptor.

How the study worked

In-vitro study. Cultured cardiomyocytes and endothelial cells exposed to serum starvation or doxorubicin to induce apoptosis. Both ghrelin forms tested for survival signaling (ERK1/2, PI3K/Akt) and apoptosis inhibition.

What this study cannot tell us

In-vitro cell culture study. The des-acyl ghrelin receptor has not been identified. In-vivo cardioprotective significance not established.

How to read the evidence

Moderate in-vitro evidence with clear mechanistic pathway identification and the novel finding of GHS-R-independent activity.

When this study was published

Published in 2002. Des-acyl ghrelin's biological activities have been further confirmed, with ongoing search for its specific receptor.

The bigger picture

Des-acyl ghrelin was considered an inactive waste product. This study reveals it's actually a cardiovascular protective molecule working through its own receptor — a major paradigm shift in ghrelin biology.

Questions still open

  • What is the receptor for des-acyl ghrelin's cardiovascular effects?
  • Does circulating des-acyl ghrelin protect the heart in vivo?
  • Could des-acyl ghrelin be developed as a cardioprotective drug without GH/appetite side effects?

Common questions

What is des-acyl ghrelin?
Most ghrelin in your blood lacks the fatty acid tag needed to activate the hunger/GH receptor. This 'des-acyl' form was thought to be inactive, but this study shows it protects heart cells through its own separate pathway.
Could this become a heart drug?
Potentially. Since des-acyl ghrelin doesn't activate the hunger receptor, it could protect the heart without causing increased appetite or GH release — a 'clean' cardioprotective agent.

Read the original research

Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.

The Journal of cell biology, 159(6), 1029-37

View on PubMed ↗

Citation

Baldanzi, Gianluca; Filigheddu, Nicoletta; Cutrupi, Santina; Catapano, Filomena; Bonissoni, Sara; Fubini, Alberto; Malan, Daniela; Baj, Germano; Granata, Riccarda; Broglio, Fabio; Papotti, Mauro; Surico, Nicola; Bussolino, Federico; Isgaard, Jorgen; Deghenghi, Romano; Sinigaglia, Fabiola; Prat, Maria; Muccioli, Giampiero; Ghigo, Ezio; Graziani, Andrea. (2002). Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.. The Journal of cell biology, 159(6), 1029-37.