Lysophospholipids in coronary artery and chronic ischemic heart disease

Abstract

Purpose of review The bioactive lysophospholipids, lysophosphatidic acid (LPA) and sphingosine 1 phosphate (S1P) have potent effects on blood and vascular cells. This review focuses their potential contributions to the development of atherosclerosis, acute complications, such as acute myocardial infarction, and chronic ischemic cardiac damage. Recent findings Exciting recent developments have provided insight into the molecular underpinnings of LPA and S1P receptor signaling. New lines of evidence suggest roles for these pathways in the development of atherosclerosis. In experimental animal models, the production, signaling and metabolism of LPA may be influenced by environmental factors in the diet that synergize to promote the progression of atherosclerotic vascular disease. This is supported by observations of human polymorphisms in the lysophospholipid metabolizing enzyme, PPAP2B, that are associated with risk of coronary artery disease and myocardial infarction. S1P signaling protects from myocardial damage that follows acute and chronic ischemia both by direct effects on cardiomyocytes and through stem cell recruitment to ischemic tissue. Summary This review will suggest novel strategies to prevent the complications of coronary artery disease by targeting LPA production and signaling. Additionally, ways in which S1P signaling pathways may be harnessed to attenuate ischemia-induced cardiac dysfunction will be explored.

Mitochondrial ROS, uncoupled from ATP synthesis, determine endothelial activation for both physiological recruitment of patrolling cells and pathological recruitment of inflammatory cells

“…The prominent roles of LPLs in chronic inflammatory disorders such as coronary artery disease (CAD), hypertension, atherosclerosis and severe vascular diseases are well established 17–20. 18, 19 In our recent report, we proposed a conceptually innovative paradigm that G-protein-coupled receptors (GPCRs) of LPLs can be classified as novel conditional DAMP receptors for the following reasons 13 : (1) LPLs are elevated during cellular stress or under stimulation by cardiovascular risk factors 21 ; (2) Basal level of LPLs mediate normal cellular functions while elevated LPLs initiate signaling cascade to either activate or dampen innate immune responses via LPL-GPCRs; (3) The expression of anti-inflammatory LPLs and their receptor are also elevated in response to inflammation and may play a role in resolution of inflammation; and we designate such LPL receptors as homeostasis-associated molecular patterns (HAMPs); and (4) LPL receptors and classically DAMP receptors reciprocally regulate the expression of each other, which is responsible for either progression or resolution of inflammation 13 . Thus, LPL receptors serve as conditional DAMP receptors by modulating physiological activities and housekeeping functions under normal conditions, while contributing to DAMP-mediated signaling pathways during cellular stress.…”

Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential

“…The role of LPLs in chronic inflammatory disorders such as coronary artery disease (CAD), hypertension [18,19], atherosclerosis and severe vascular diseases is well established [20,21]. Furthermore, LPLs contribute to pathophysiology of autoimmune disorders such as rheumatoid arthritis, and is involved in exacerbating the progression of the disease [22,23].…”

Model-based clustering of multi-tissue gene expression data

“…Metabolism-related clusters 6 and 7 were found to be regulated by genes AGXT2 and SPP2, in SF and VF respectively. AGXT2 polymorphisms were identified as risk for CAD in Asian populations [59,57], and SPP2 may contribute to the atheroprotective effects of HDL [1]. These clusters may also be regulated by AADAC in SM, that controls the export of sterols [53].…”