Loading…
LPA 2 Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction
Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role...
Saved in:
Published in: | Circulation research 2022-08, Vol.131 (5), p.388-403 |
---|---|
Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role of LPA and its receptors in MI is less understood.
To study the unknown role of LPA and its receptors in heart during MI.
In this study, we found that mice also had elevated LPA level in peripheral blood, as well as increased cardiac expression of its receptor LPA
in the early stages after MI. With adult and neonate MI models in global
knockout (
-KO) mice, we found
deficiency increased vascular leak leading to disruption of its homeostasis, so as to impaired heart function and increased early mortality. Histological examination revealed larger scar size, increased fibrosis, and reduced vascular density in the heart of
-KO mice. Furthermore,
-KO also attenuated blood flow recovery after femoral artery ligation with decreased vascular density in gastrocnemius. Our study revealed that
was mainly expressed and altered in cardiac endothelial cells during MI, and use of endothelial-specific
knockout mice phenocopied the global knockout mice. Additionally, adenovirus-
and pharmacologically activated LPA
significantly improved heart function, reduced scar size, increased vascular formation, and alleviated early mortality by maintaining vascular homeostasis owing to protecting vessels from leakage. Mechanistic studies demonstrated that LPA-LPA
signaling could promote endothelial cell proliferation through PI3K-Akt/PLC-Raf1-Erk pathway and enhanced endothelial cell tube formation via PKD1-CD36 signaling.
Our results indicate that endothelial LPA-LPA
signaling promotes angiogenesis and maintains vascular homeostasis, which is vital for restoring blood flow and repairing tissue function in ischemic injuries. Targeting LPA-LPA
signal might have clinical therapeutic potential to protect the heart from ischemic injury. |
---|---|
ISSN: | 0009-7330 1524-4571 |
DOI: | 10.1161/CIRCRESAHA.122.321036 |