Lipoprotein lipase (LPL) is a lipolytic enzyme involved in catalyzing the hydrolysis of triglycerides (TG) in chylomicrons and very low-density lipoprotein (VLDL) particles. Over the last decade, the clinical significance of measuring LPL mass without heparin injection has been increasingly studied. In earlier studies, it was shown that this marker was utilized to classify type 1 hyperlipoproteinemia, which is an extremely rare metabolic disorder. Later, researchers paid more attention to the clinical significance of measuring this parameter in more common metabolic disorders. Studies have shown that pre-heparin plasma LPL mass has significant relationships with serum lipid and lipoproteins, visceral fat area, and even a marker for acute inflammation, although this might be a metabolic surrogate marker which does not appear to be involved in catalyzing the hydrolysis of TG in TG-rich lipoproteins. We suggest that pre-heparin LPL mass in plasma or sera provides us with useful and important information on the pathophysiology of metabolic disorders or acute inflammation despite its simplicity from a practical point of view.
Elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, hallmarks of the atherogenic lipid profile found in the metabolic syndrome and type 2 diabetes, are commonly seen in Japanese patients with coronary heart disease (CHD). In the setting of mildly to moderately elevated plasma TG (150−500 mg/dl), very-low-density lipoprotein (VLDL) accumulates and so do high levels of atherogenic TG-rich, cholesterol-enriched remnant particles. Indeed, in hypertriglyceridemia, abnormalities are seen in the quantity and quality of all lipoprotein B−containing lipoproteins. Non−HDL-C (total cholesterol minus HDL-C) provides a convenient measure of the cholesterol content of all atherogenic lipoproteins, and thus incorporates the potential risk conferred by elevated levels of atherogenic TG-rich remnants that is additional to the risk associated with low-density lipoprotein cholesterol (LDL-C). Non−HDL-C level has been found to be a strong predictor of future cardiovascular risk among patients whether or not they exhibit symptoms of vascular disease, and was recently recommended as a secondary treatment target (after LDL-C) in patients with elevated TG by the National Cholesterol Education Program Adult Treatment Panel III. Adoption of this readily available measure to assess risk and response to treatment in patients with elevated TG would improve treatment of dyslipidemia in a substantial number at risk for CHD.
CX3CL1/fractalkine is a chemokine with a unique CX3C motif. Fractalkine is synthesized in endothelial cells as a membrane protein, and the N-terminal domain containing a CX3C motif is cleaved and secreted. CX3CR1, the specific receptor for fractalkine, is expressed in monocytes and lymphocytes. Membrane-bound fractalkine works as an adhesion molecule for these leukocytes and the secreted form as a chemotactic factor. Fractalkine is produced by endothelial cells stimulated with tumor necrosis factor-α, interleukin-1 (IL-1), lipopolysaccharide and interferon-γ. Expression of fractalkine in endothelial cells is inhibited by the soluble form of IL-6 receptor-α, 15-deoxy-Δ12,14-prostaglandin J2, and hypoxia. The expression of fractalkine is tightly regulated and fractalkine plays an important role in the interaction between leukocytes and endothelial cells.
In a recent paper, we reported that pravastatin sodium (pravastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme. A reductase, decreases the concentrations of low density lipoprotein (LDL) cholesterol through an LDL receptor pathway in Japanese White (JW) rabbits, whereas this agent lowers high density lipoprotein (HDL) cholesterol in a manner correlated with a reduction of very low density lipoprotein (VLDL) cholesterol secretion from the liver. In the present study, we administered pravastatin to JW rabbits at 30 mg/kg for 14 days and examined further the mechanisms for the reduction of HDL cholesterol. A striking finding was that the 4-day administration of pravastatin at 30 mg/kg selectively decreased the concentration of HDL cholesterol. Since 4-day administration of pravastatin to JW rabbits did not change the concentrations of hepatic LDL receptor proteins, these receptors were not likely to be involved in the reduction of HDL cholesterol. Another important finding was that pravastatin suppressed VLDL cholesteryl ester (CE) secretion from the liver, but not that of other VLDL lipids and VLDL proteins, indicating that the CE-poor VLDL particles were secreted by the consecutive administration of pravastatin. There were, however, no differences in the levels of VLDL cholesterol between the control and pravastatin-treated groups over the experimental period of 14 days. These observations raised the possibility that the reduction of HDL cholesterol in the pravastatin-treated group was due to the transfer of CE molecules from HDL particles to these CE-poor VLDL particles. Molecular species analysis supported this notion that the VLDL-CE in the pravastatin-treated group was rich in cholesteryl linoleate, indicating that the CE in this group mainly originated from HDL, whereas the VLDL-CE in the control group was rich in cholesteryl oleate, indicating that the CE in this group originated from the liver. The present study suggests that pravastatin lowers HDL cholesterol by transferring CE from these lipoproteins to VLDL in JW rabbits.
Since increased leukocytes within days after the onset of acute myocardial infarction (AMI) may reflect an increased expression of the adhesion molecules necessary for effective endothelial transmigration, we evaluated the expression of adhesion molecules on leukocytes throughout the acute phase of MI. We measured the number of leukocytes and enzymes and the expression levels of CD11a, CD18, very-late-after-activation antigen-4α, intracellular adhesion molecule-1 (ICAM-1) and L-selectin by flow cytometry before and after coronary intervention, and at 6, 12, 18, 48 and 72 hours of MI in 5 patients (AMI group). As controls, we measured these parameters in 5 patients who had been diagnosed with angina pectoris and underwent coronary intervention (AP group). In the AMI group the expression of monocyte CD11a was significantly increased after 6 hours, and CD18 and ICAM-1 expression were also significantly increased after 12 hours, whereas that of monocyte L-selectin was increased after 72 hours. In addition, the increased monocyte CD11a was accompanied by an increased number of monocytes and a greater expression of CD11a per cell in the AMI group. In conclusion, since CD11a and CD18 are expressed on the cell surface as a heterodimer and ICAM-1 is a ligand for CD11a/CD18, their increased expression may contribute to their adhesion to endothelium in ischemic regions and may lead to the formation of microaggregates.