Role of Lysophosphatidylcholine (LPC) in Atherosclerosis

Abstract

Lysophosphatidylcholine (LPC) is a bioactive proinflammatory lipid generated by pathological activities. LPC is also a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL) and is implicated as a critical factor in the atherogenic activity of Ox-LDL. LPC is believed to play an important role in atherosclerosis and inflammatory diseases by altering various functions in a number of cell-types, including endothelial cells, smooth muscle cells, monocytes, macrophages, and T-cells. LPC activates several second messengers -- including protein kinase C, extracellular-signal-regulated kinases, protein tyrosine kinases, and Ca(2+) -- implicating the engagement of transduction mechanisms in its observed actions. Moreover, recent evidence suggests that in several cell-types, cloned orphan G-protein-coupled receptors may serve as the specific receptors via which LPC modulates second messenger pathways (although LPC may not be a direct ligand of such receptors). In addition, current evidence suggests that LPC impairs the endothelium-dependent relaxations mediated by endothelium-derived relaxing factors and directly modulates contractile responses in vascular smooth muscle. However, despite all this, and although elevated levels of LPC have been linked to the cardiovascular complications associated with atherosclerosis, ischemia, and diabetes, the precise pathophysiological roles played by LPC in several states remain to be established. In this review, we focus in some detail on the entirety of the signal-transduction system for LPC, its pathophysiological implications, and the vascular abnormalities associated with it.

Imaging of Lysophosphatidylcholine in Human Coronary Plaques by Color Fluorescence Angioscopy

“…2) impairs endothelin-induced vascular relaxation; 7) and induces release of IL-6, IL-8, and arachidonic acid from vascular smooth muscle cells.…”

“…( and frequently induces fatal diseases such as acute coronary syndromes and cerebral events. Lysophosphatidylcholine (LPC) is a proinflammatory substance, and it is the major bioactive phospholipid component of oxidized low-density lipoprotein and plays a critical role in the atherogenic activity of oxidized low-density lipoprotein.2) This substance is generated by lipoprotein-associated phospholipase A2;3) induces vascular endothelial cell dysfunction; 4) causes endothelial cell apoptosis by DNA fragmentation; 5) stimulates adhesion and activation of lymphocytes and initiates chemotaxis of macrophages; 6) causes transformation of vascular smooth muscle cells that is characteristic of atherosclerosis;2) impairs endothelin-induced vascular relaxation; 7) and induces release of IL-6, IL-8, and arachidonic acid from vascular smooth muscle cells.2) It is well known that this detrimental substance is abundantly contained in human atherosclerotic lesions, 8) and it is released from human coronary vessels in vivo. …”

“…2) This substance is generated by lipoprotein-associated phospholipase A2; 3) induces vascular endothelial cell dysfunction; 4) causes endothelial cell apoptosis by DNA fragmentation; 5) stimulates adhesion and activation of lymphocytes and initiates chemotaxis of macrophages; 6) causes transformation of vascular smooth muscle cells that is characteristic of atherosclerosis; 2) impairs endothelin-induced vascular relaxation; 7) and induces release of IL-6, IL-8, and arachidonic acid from vascular smooth muscle cells.…”

Dietary Phospholipids and Phytostrerols: A Review on Some Nigerian Vegetable Oils

“…LPC is believed to play an important role in atherosclerosis and inflammatory diseases by altering various functions in a number of cell-types, including endothelial cells, smooth muscle cells, monocytes, macrophages, and T-cells. It activates several second messengers and impairs the endothelium-dependent relaxations mediated by endothelium-derived relaxing factors and directly modulates contractile responses in vascular smooth muscle [74]. Phosphatidylinositol (PI) plays a key role in the membrane recruitment and/or activation of proteins [75].…”

Effects of lysophosphatidylcholine on β-amyloid-induced neuronal apoptosis

“…The biological effects and signaling properties of LPC have been extensively studied in atherosclerosis-related cells [9] . LPC can induce neuronal sheath demyelination, axonal degeneration and neuronal apoptosis [10,11] , which are common pathological characteristics of neurodegenerative diseases [12,13] .…”