Potential role of lysophosphatidic acid in hypertension and atherosclerosis.
BACKGROUND
Lysophosphatidic acid (LPA) is present in both serum and cytosol. Serum LPA is mainly released from platelets whereas cytosolic LPA is the metabolite of phosphatidic acid due to the action of phopholipase A2. Because platelet function and phospholipase A2 activity are upregulated in hypertensive and coronary heart disease patients, respectively, plasma and cytosolic LPA levels are expected to be higher in these pathological conditions.


METHODS
LPA is known to cause platelet aggregation and thus release more LPA as well as platelet-derived growth factor; this positive feedback circuit leads to the continuous growth of vascular smooth muscle cells (VSMCs). LPA also increases the intracellular concentration of free calcium in VSMCs and elevates the blood pressure. LPA content in the atherosclerotic plaque is elevated about 13 times in comparison with normal tissues because oxidized low-density lipoproteins promote the production of LPA. On the other hand, LPA has been shown to protect the heart from ischemia and reperfusion-induced damage due to its antiapoptosis effect. Because LPA has been reported to stimulate mitogen-activated protein kinase, phosphatidylinositide-3-kinase and protein kinase C, this bioactive phospholipid may be involved in the signal transduction mechanisms during the process of cardiac hypertrophy.


CONCLUSIONS
Due to its ability to increase intracellular Ca2+ and proliferation of VSMCs, LPA may play an important role in the development of hypertension and atherosclerosis. It is therefore suggested that LPA antagonists may prove useful in the treatment of both hypertension and atherosclerosis.
Xu
Yan-Jun
YJ
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Canada.
Aziz
Osama A
OA
Bhugra
Praveen
P
Arneja
Amarjit S
AS
Mendis
Maleen R
MR
Dhalla
Naranjan S
NS
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D002320:Cardiovascular Physiological Phenomena; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008246:Lysophospholipids / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D008246:Lysophospholipids; D019204:GTP-Binding Proteins