TITLE:
Direct anti-atherosclerotic therapy preventing intracellular cholesterol retention
AUTHORS:
Alexander N. Orekhov
KEYWORDS:
Allicor; Anti-Atherosclerotic Therapy; Atherosclerosis; Cell Culture; Drugs; Imaging; Intracellular Cholesterol Retention; Natural Products
JOURNAL NAME:
Health,
Vol.5 No.7A,
July
16,
2013
ABSTRACT:
The key initiating
process in atherogenesis is the
subendothelial cholesterol retention, which is both necessary and
sufficient to provoke lesion initiation. Retention of cholesterol transported
by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is
an absolute requirement for lesion development. This allows us to consider intracellular
cholesterol retention as a novel target for anti-atherosclerotic therapy. In
this case, the target is not the level of blood cholesterol but the level of
cholesterol in vascular cells. This review summarizes the results of our
basic studies shedding light on the mechanisms
of intracellular cholesterol retention. We describe our cellular models to
search for anti-atherosclerotic agents and demonstrate the use of these models
for the development of anti-atherosclerotic drugs. We use natural products as
the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy
should be long-term or even lifelong. Using cellular models and natural
products, we have developed an approach to prevent intracellular cholesterol
retention in cultured subendothelial aortic cells. We have developed drugs that
reduce intracellular cholesterol retention, namely Allicor on the basis of
garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet)
possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic
powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in
postmenopausal women. Thus, the main findings of our basic research have been
successfully translated into clinics. As a result, this translation, a novel approach
to the development of anti-atherosclerotic therapy, has been established. Our
clinical trials have confirmed the suitability of innovative approach and the
efficacy of novel drugs developed on the basis our methodology.