TITLE:
Intracellular Cholesterol Retention—New Target for Direct Anti-Atherosclerotic Therapy
AUTHORS:
Alexander N. Orekhov
KEYWORDS:
Allicor; Anti-Atherosclerotic Therapy; Atherosclerosis; Cell Culture; Drugs; Imaging; Natural Products
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.3 No.4A,
July
23,
2013
ABSTRACT: Accumulation of cholesterol in arterial
cells, intracellular cholesterol retention, may be responsible for all major
manifestations of atherosclerosis on a cellular level. Previously we have shown that
intracellular cholesterol retention is the principal event in the genesis of
atherosclerotic lesions. This allows us to consider cellular retention of cholesterol
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 describes our approach based on the use of cultured human
arterial cells for the development of direct anti-atherosclerotic therapy. We
use natural products as the basis of promising drugs for anti-atherosclerotic
therapy. Using natural products, we have developed an approach to prevent
intracellular cholesterol retention in cultured cells. Our knowledge of the
mechanisms of atherosclerosis is the foundation on which we have developed
drugs that have a direct anti-atherosclerotic effect, 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 has a direct anti-atherosclerotic effect on carotid atherosclerosis
in asymptomatic men. Karinat prevents the development of carotid
atherosclerosis in postmenopausal women. Thus, the main findings of our basic
research have been successfully translated into clinical practice. 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.