In literature, many beneficial effects of HDL on macrophages have been described. Nonetheless, the HDL concentrations that are being used (25-100µg/ml) in almost every study don't seem to be highly relevant for the in vivo situation (e.g. 40-60mg/dl or 400-600µg/ml). Why not use the relevant concentrations? Could the HDL become toxic when you add it to the cells in these physiological (or even higher) concentrations?
HDL concentration used in the in vitro research is in units of protein per ml (100 µg HDL protein/ml). Unfortunately, these are not the units that clinicians in the U.S. typically use. 100µg HDL protein per ml corresponds to ~40µg total cholesterol per ml, which is 4000 µg cholesterol per 100 ml = 4.0 mg/dl. A typical plasma concentration in healthy subjects would be about 10 times greater (40 mg/dl).
By the way, HDL from healthy is not toxic, but one may not want to use too high concentration!
I agree with Liu. the difference between the quoted concentrations is that the first one is expressed in whole HDL particle in mc/mL while circulating plasma HDL is expressed in Cholesterol-HDL mg/dL ,being cholesterol one of the numerous components of HDL.
Cholesterol efflux experiments try to reproduce what happens in the arterial intima, where macrophage foam cells are formed. In the intimal fluid the concentration of HDL is much lower than in serum, although in the intima the particle composition and quality may also change.
For better understanding the difference between plasma concentration of HDL-Cholesterol and other studies on the role of HDL particle in cardiovascular diseases, please read our papers in my profile in Research Gate and other authors, on variability of HDL particle and associated enzymes like paraoxonase, lecithin cholesterol acyl transferase, Cholesterol ester transfer protein ( CETP), structural Apolipopoteins Apo Ai and Apo AII. All of them are included in Topics as Clinical Biochemistry, and Atherogenic mechanisms . There are many studies about its activity protecting LDL from oxidation, the enriched tryglycerides- HDL particle and its own oxidation, its immunological activity and metabolic syndrome In this paragraph you will find numerosous key words
1. As Miriam above stated, the concentration of HDL in the arterial wall is much lower. 2. Another factor is that receptors for cholesterol efflux are saturated at concentrations above 100µg/ml. In terms of cholesterol efflux, you can use low concentration to measure cholesterol efflux correctly. G. Rothblat has a variety of excellent papers on cholesterol efllux and dosing effects. 3. A third issue is the availability of HDL, if you before a clinical study you will be limited in HDL you can use. Therefore, you will try to use lower concentrations.
If your question is about the comparison of HDL particle concentrations, then two numbers differ ten times because 1ml/dl is 10 micrograms/ml. If you perform in vitro experiments with lipoproteins you must be careful because they tend to form aggregates if the concentration is high.
As discussed by the other respondents, the concentration of HDL "seen" by tissues is substantially lower than circulating levels. As reviewed by my late mentor (Paul Roheim) and co-workers (Sloop CH, Dory L, Roheim PS. 1987. Interstitial fluid lipoproteins. J Lipid Res. 28(3):225-37) the average concentration ratio of interstitial fluid to plasma for apoA-I (the major HDL protein) is between (0.07 to 0.12). Thus, with a plasma HDL-C level of 50 mg/dl, this roughly translates into an HDL protein level of ~125 mg/dl or 1,250 ug/ml. Taking into account the interstitial fluid/plasma ratio, the effective HDL protein concentration that a typical cell would see is around 125 ug/ml - which is close to the concentrations used in cell culture.
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