Serum atherogenicity testing on cell cultures: published data questioned
In the large series of publications started in the 1980s (1) and
continued until today, discussion and references in (2,3), was reported
that culturing of smooth muscle cells with the serum from patients with
coronary heart disease caused lipid infiltration of cultured cells, while
serum from healthy individuals had no such effect. Cell cultures were used
for testing of drugs and food components. Numerous substances were
reported either pro- or anti-atherogenic (2). Clinical recommendations
were formulated on the basis of cell culture experiments including dosage
of drugs (4). However, according to generally accepted knowledge, anti-
atherogenic or lipid-lowering agents can influence cholesterol synthesis,
lipid metabolism in the liver, intestinal absorption or endothelium-
related mechanisms. All these targets are absent in cell cultures.
Inflammatory mechanisms are also not reproduced. In vivo, relationship
between cholesterol uptake by cells and atherogenesis is inverse rather
than direct: for example, in familial hypercholesterolemia caused by
abnormality of cellular LDL-receptors, inefficient clearance of LDL from
blood causes hypercholesterolemia and is associated with predisposition to
atherosclerosis. Accordingly, if a pharmacological agent reduces
cholesterol uptake by cells in vitro, it should be expected to cause
cholesterol elevation in vivo. Unreliability of conclusions and
recommendations discussed above can be proven by reductio ad absurdum:
pharmacological agents which are “anti-atherogenic” in a cell culture
should be expected to be pro-atherogenic in vivo.
References
1. Chazov EI, Tertov VV, Orekhov AN, Lyakishev AA, Perova NV,
Kurdanov KA, et al. Atherogenicity of blood serum from patients with
coronary heart disease. Lancet 1986; 2:595-8.
2. Jargin SV. Testing of anti-atherogenic drugs and food components
on cell cultures: assessment of reliability. P R Health Sci J 2010; 29:86-
7.
4. Orekhov AN, Pivovarova EM, Sobenin IA, Yakushkin VV, and Tertov
VV. Use of cell culture for optimisation of direct antiatherogenic therapy
with verapamil. Drugs 1992; 44 Suppl 1:105-10.
Rapid Response:
Serum atherogenicity testing on cell cultures: published data questioned
In the large series of publications started in the 1980s (1) and
continued until today, discussion and references in (2,3), was reported
that culturing of smooth muscle cells with the serum from patients with
coronary heart disease caused lipid infiltration of cultured cells, while
serum from healthy individuals had no such effect. Cell cultures were used
for testing of drugs and food components. Numerous substances were
reported either pro- or anti-atherogenic (2). Clinical recommendations
were formulated on the basis of cell culture experiments including dosage
of drugs (4). However, according to generally accepted knowledge, anti-
atherogenic or lipid-lowering agents can influence cholesterol synthesis,
lipid metabolism in the liver, intestinal absorption or endothelium-
related mechanisms. All these targets are absent in cell cultures.
Inflammatory mechanisms are also not reproduced. In vivo, relationship
between cholesterol uptake by cells and atherogenesis is inverse rather
than direct: for example, in familial hypercholesterolemia caused by
abnormality of cellular LDL-receptors, inefficient clearance of LDL from
blood causes hypercholesterolemia and is associated with predisposition to
atherosclerosis. Accordingly, if a pharmacological agent reduces
cholesterol uptake by cells in vitro, it should be expected to cause
cholesterol elevation in vivo. Unreliability of conclusions and
recommendations discussed above can be proven by reductio ad absurdum:
pharmacological agents which are “anti-atherogenic” in a cell culture
should be expected to be pro-atherogenic in vivo.
References
1. Chazov EI, Tertov VV, Orekhov AN, Lyakishev AA, Perova NV,
Kurdanov KA, et al. Atherogenicity of blood serum from patients with
coronary heart disease. Lancet 1986; 2:595-8.
2. Jargin SV. Testing of anti-atherogenic drugs and food components
on cell cultures: assessment of reliability. P R Health Sci J 2010; 29:86-
7.
3. Jargin SV. Cell culture as a testing system for anti-atherogenic
substances: a brief communication. Acta Pharm Sci 2008;50(3):237-40.
http://www.actapharmasciencia.org/actapharmasciencia.org/pdf/9Cell%20Cul...
4. Orekhov AN, Pivovarova EM, Sobenin IA, Yakushkin VV, and Tertov
VV. Use of cell culture for optimisation of direct antiatherogenic therapy
with verapamil. Drugs 1992; 44 Suppl 1:105-10.
Competing interests:
None declared
Competing interests: No competing interests