Myeloperoxidase Oxidized LDL Interferes with Endothelial Cell Motility through miR-22 and Heme Oxygenase 1 Induction: Possible Involvement in Reendothelialization of Vascular Injuries

Abstract

Cardiovascular disease linked to atherosclerosis is the leading cause of death worldwide. Atherosclerosis is mainly linked to dysfunction in vascular endothelial cells and subendothelial accumulation of oxidized forms of LDL. In the present study, we investigated the role of myeloperoxidase oxidized LDL (Mox-LDL) in endothelial cell dysfunction. We studied the effect of proinflammatory Mox-LDL treatment on endothelial cell motility, a parameter essential for normal vascular processes such as angiogenesis and blood vessel repair. This is particularly important in the context of an atheroma plaque, where vascular wall integrity is affected and interference with its repair could contribute to progression of the disease. We investigated in vitro the effect of Mox-LDL on endothelial cells angiogenic properties and we also studied the signalling pathways that could be affected by analysing Mox-LDL effect on the expression of angiogenesis-related genes. We report that Mox-LDL inhibits endothelial cell motility and tubulogenesis through an increase in miR-22 and heme oxygenase 1 expression. Our in vitro data indicate that Mox-LDL interferes with parameters associated with angiogenesis. They suggest that high LDL levels in patients would impair their endothelial cell capacity to cope with a damaged endothelium contributing negatively to the progression of the atheroma plaque.

Apoliporotein L3 interferes with endothelial tube formation via regulation of ERK1/2, FAK and Akt signaling pathway

“…Thrombin also induced angiogenesis in endothelial cells [37]. On the other hand inflammatory stimuli can also impede angiogenic processes [38]. These reports combined with our observations that VEGF and FGF, two well characterized pro-angiogenic stimulators [39] induced APOL3 expression in HMEC-1, lead us to investigate the possible functional role of APOL3 in the angiogenic process.…”

Other forms of oxidized LDL: Emerging functions (Review)

“…where CuOx-LDLs are known to trigger cell death, which was not observed with Mox-LDLs (19). Similarly, the author demonstrated that Mox-LDLs decrease cell migration, wound healing and tubulogenesis in human umbilical vein endothelial cells, while the opposite has been recently demonstrated using the other model of LDL oxidation in human coronary artery smooth muscle cells (19,20). The treatment of HUVECs with physiological serum concentrations of Mox-LDL was shown to significantly decrease (up to 50%) the ability of the cells to form tubules on Matrigel (19).…”

The Effect of Metformin Monotherapy on Biochemical Parameters Associated With Diabetes Mellitus, Kidney, Cardiac, Liver, Thyroid, and Reproductive Organ Functions in Pre- And Post-Menopause Women With Type 2 Diabetes Mellitus

“…CVD has been found to be linked to an oxidized form of LDL-c and a role for myeloperoxidase oxidized (MOX-LDL) LDL-c dysfunction may be the cause for CVD risk. MOX-LDL may interfere with some parameters associated with angiogenesis leading to high LDL-c levels, and in some patients, it may impair the endothelial cell function which may contribute to negative progression of the atheroma plague [13].…”

“…Current guideline recommends aggressive strategic treatment to reduce LDL-c, but in our study simple use of MMT, which is a good medication has improved LDL-c reducing all complications associated with cardiac functions. Among HDL-c and LDL-c, the former should increase, and the later decrease and every 10 mg/dL increase in LDL-c are associated with 12% increase in CVD [12,13].…”

“…This study outcome is unable to explain this unusual findings but future studies are showing extended time after 12 months could possible establish the reasons and, may be the ratios will improve after 12 months of treatment. Previous studies have shown a correlation between LDL/HDL ratio to thyroid hormones, but we did not undertake this comparison [13][14][15].…”