Lysophosphatidic acid enhances neointimal hyperplasia following vascular injury through modulating proliferation, autophagy, inflammation and oxidative stress

Abstract

Lysophosphatidic acid (LPA), which is one of the intermediate products of membrane phospholipid metabolism, is a bioactive phospholipid that possesses diverse activities. In the present study, the effects of LPA on neointimal formation following vascular injury were investigated. A carotid artery balloon injury model was employed in the present study, and following vascular injury, rats received an intraperitoneal injection of 1 mg/kg LPA. Subsequently, histopathological alterations were assessed by hematoxylin and eosin staining, the expression levels of proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry, apoptosis was assessed via a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and the expression levels of apoptosis-associated and autophagy-associated proteins were detected by western blotting. In addition, inflammatory and oxidative stress-associated factors were assessed by reverse transcription-quantitative polymerase chain reaction or corresponding kits. The results of the present study demonstrated that LPA enhanced vascular injury-induced neointimal hyperplasia. LPA further elevated the expression levels of PCNA in the injured carotid artery tissues. LPA exhibited no effect on apoptosis in carotid artery tissues, whereas it modulated autophagy in the injured carotid artery tissues. Furthermore, LPA enhanced vascular injury-induced inflammation and oxidative stress. The present study demonstrated that LPA may enhance neointimal hyperplasia following vascular injury by modulating proliferation, autophagy, inflammation and oxidative stress, but not apoptosis. Furthermore LPA may contribute to the pathology of atherosclerosis and may be considered a promising therapeutic target for the treatment of atherosclerosis.

The Number of Platelets in Patient’s Blood Influences the Mechanical and Morphological Properties of PRP-Clot and Lysophosphatidic Acid Quantity in PRP

“…We found that this lipid by-product of autotaxin activity is involved in cancer, vascular defects, and neural tissue but is largely unexplored in the immune system. In blood vessels, LPA enhanced neo-intimal hyperplasia following vascular injury by modulating proliferation, autophagy, inflammation, and oxidative stress and may contribute to the pathology of atherosclerosis [37] whereas, in liver, can block the pathogenesis of acute liver injury decreasing inflammatory cytokines [38]. In glial cells through its receptor, LPA protects from oxidative stress [39] and exerts antiaging effect in age-related diseases by improving the anti-oxidative ability of yeast cells [40].…”

Lysophosphatidic Acid Is Associated With Cardiac Dysfunction and Hypertrophy by Suppressing Autophagy via the LPA3/AKT/mTOR Pathway

“…LPA, as a phospholipid signaling molecule, which is produced from circulating lysophosphatidylcholine (LPC) by ATX, is involved in multiple cardiovascular diseases ( Smyth et al, 2014 ; Chen et al, 2017 ; Gu et al, 2017 ; Nsaibia et al, 2017 ; Shen et al, 2018 ). It has been reported that LPA is present in abundance in the serum of patients with an acute myocardial infarction (AMI) ( Chen et al, 2003 ), and LPA1 and LPA3 receptor protein levels are increased in the ischemic heart that develops cardiac remodeling, implying that LPA plays a role in cardiac remodeling after a MI.…”

“…Previous evidence has shown that LPA inhibits autophagy in starvation-induced cancer cells ( Chang et al, 2007 ). Recently, LPA has been reported to promote neointimal hyperplasia after vascular injury by regulating autophagy ( Shen et al, 2018 ). In the present study, the results showed that LPA suppresses activation of autophagy in vivo and in vitro .…”

“…Regulation of myocyte autophagy in cardiac remodeling, such as myocyte hypertrophy, is not fully understood. It has been reported that LPA inhibits autophagy in starvation-induced cancer cells ( Chang et al, 2007 ) and in injured carotid artery tissues ( Shen et al, 2018 ). Moreover, LPA is capable of regulating activation of the mammalian target of rapamycin (mTOR) pathway ( Kam and Exton, 2004 ; Lee et al, 2016 ), which negatively mediates autophagy in various cells.…”

Exosomal LINC01005 derived from oxidized low‐density lipoprotein‐treated endothelial cells regulates vascular smooth muscle cell phenotypic switch

“…1 The proliferation and migration of vascular smooth muscle cells (VSMCs) into the intima is the key pathological basis of AS. 2 In response to vascular injury, VSMCs undergo a phenotypic transition from a contractile (also termed differentiated) state to a synthetic (also termed dedifferentiated) state and subsequently maintain abnormal proliferation, migration, and matrix synthesis, contributing to AS. 3,4 Thus, therapeutic targeting aimed at promoting beneficial changes in VSMC phenotype may be a viable strategy of treating AS.…”