Monocytic Cell Adhesion to Oxidised Ligands: Relevance to Cardiovascular Disease

Abstract

Atherosclerosis, the major cause of vascular disease, is an inflammatory process driven by entry of blood monocytes into the arterial wall. LDL normally enters the wall, and stimulates monocyte adhesion by forming oxidation products such as oxidised phospholipids (oxPLs) and malondialdehyde. Adhesion molecules that bind monocytes to the wall permit traffic of these cells. CD14 is a monocyte surface receptor, a cofactor with TLR4 forming a complex that binds oxidised phospholipids and induces inflammatory changes in the cells, but data have been limited for monocyte adhesion. Here, we show that under static conditions, CD14 and TLR4 are implicated in adhesion of monocytes to solid phase oxidised LDL (oxLDL), and also that oxPL and malondialdehyde (MDA) adducts are involved in adhesion to oxLDL. Similarly, monocytes bound to heat shock protein 60 (HSP60), but this could be through contaminating lipopolysaccharide. Immunohistochemistry on atherosclerotic human arteries demonstrated increased endothelial MDA adducts and HSP60, but endothelial oxPL was not detected. We propose that monocytes could bind to MDA in endothelial cells, inducing atherosclerosis. Monocytes and platelets synergized in binding to oxLDL, forming aggregates; if this occurs at the arterial surface, they could precipitate thrombosis. These interactions could be targeted by cyclodextrins and oxidised phospholipid analogues for therapy.

Poly-(ADP-ribose) polymerases inhibition by olaparib attenuates activities of the NLRP3 inflammasome and of NF-κB in THP-1 monocytes

“…The adhesion of monocytes to the vascular endothelium is important in the initiation and progression of atherosclerosis [27]. OxLDL markedly increased the adhesion of monocytes to HUVEC monolayers and this was decreased by either olaparib or MCC950 (Fig 6A).…”

Associations Among Microvascular Dysfunction, Fatty Acid Metabolism, and Diabetes

“…Importantly, the interaction between MDA and proteins or amino acids yields unstable carboxylation products known as advanced glycation end products, which induce oxidation and structural damage to cell membrane lipids, and negatively affect the normal functioning of the microvasculature [41]. Furthermore, studies have indicated that MDA promotes platelet aggregation, as well as the synthesis and release of thromboxane A2, and consequently stimulates platelet activation and thrombosis [42,43]. Promising prospects include inhibiting malondialdehyde production and metabolism to enhance microvascular function and alleviate complications in people with diabetes.…”

Effect of Early Heparin Anticoagulation on Blood Flow and Cardiac Function in Patients with Acute ST Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

“…Since thrombolytic therapy is limited by many factors and angiography is required to determine the extent of IRA reperfusion [6], PPCI treatment as soon as possible is the most effective reperfusion method for STEMI patients [7][8][9]. Guidelines recommend that STEMI patients start anticoagulation therapy before PPCI, which can effectively block the coagulation cascade, reduce thrombosis, inhibit the further development of thrombosis, and even promote the dissolution of coronary thrombosis and the re-opening of IRA [10]. Yet the start timing for a PPCI preoperative anticoagulant ther-apy study is less, and there is no clear early heparin anticoagulationization large clinical study of IRA recanalization.…”