Lysophosphatidic acid contributes to myocardial ischemia/reperfusion injury by activating TRPV1 in spinal cord

Basic Res Cardiol, 2024 · DOI: 10.1007/s00395-023-01031-z · Published: April 1, 2024

Cardiovascular Science Neurology Genetics

Simple Explanation

This study investigates how lysophosphatidic acid (LPA), a type of fat molecule, contributes to heart damage after a heart attack (myocardial ischemia/reperfusion injury). The researchers focused on the role of a protein called TRPV1 in the spinal cord. The study found that after a heart attack, LPA levels increase in the fluid around the spinal cord. This LPA then activates TRPV1 in the spinal cord, which worsens the heart damage. By blocking LPA from interacting with TRPV1, either through a genetic modification or a specific peptide, the researchers were able to reduce heart damage, suggesting a new way to protect the heart during a heart attack.

Study Duration

Not specified

Participants

Male adult C57BL/6J wild-type (WT) mice and TRPV1K710N knock-in mice

Evidence Level

Not specified

Key Findings

1
Myocardial I/R injury elevates CSF LPA levels, which is reduced by HA130 treatment.
2
Blocking the K710 region through K710N mutation or TRPV1 peptide resulted in reduced neuropeptides release and decreased activity of cardiac sensory neurons, leading to a decrease in cardiac norepinephrine concentration
3
Inhibiting the interaction of LPA with TRPV1 by blocking the K710 region uncovers a novel strategy for preventing myocardial ischemic injury.

Research Summary

This study provides evidence suggesting that LPA contributes to myocardial I/R injury in mice by activating TRPV1-mediated signaling in the spinal cord. The study initially showed a strong association between the elevated CSF LPA levels and myocardial ischemic injury in mice. Intrathecal administration of HA130, a substance known to decrease LPA level, effectively alleviated myocardial injury. By utilizing a TRPV1K710N knock-in mouse model as well as a TRPV1 peptide that blocks the K710 region, we further demonstrated that LPA aggravated myocardial I/R injury by activating TRPV1 via the K710 site.

Practical Implications

Therapeutic Target Identification

The K710 region of TRPV1 represents a novel therapeutic target for preventing myocardial ischemic injury.

Drug Development

Development of drugs that block the interaction between LPA and TRPV1 could offer a new approach to cardioprotection.

Biomarker Potential

CSF LPA levels could serve as a biomarker for assessing the severity of myocardial injury and guiding treatment strategies.

Study Limitations

1
The autotaxin level in the CSF was not measured.
2
The activity of cardiac sensory neurons were assessed using in vitro calcium imaging techniques, lacking electrophysiological patch clamp confirmation.
3
The study primarily focused on the intramyocardial Akt/ERK/GSK-3μ signaling pathway.

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