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Vinculin-and caldesmon-immunoreactive forms and actin isoform patterns were studied in samples of normal and atherosclerotic human aorta. After removal of adventitia and endothelium, the remaining tissue was divided into three layers: media, muscular-elastic (adjacent to media) intima, and subendothelial (juxtaluminal) intima. In media of normal aorta, meta-vinculin accounted for 41.0 ± 0.9% (mean ± SEM) of total immunoreactive vinculin (meta-vinculin + vinculin); 150-kDa caldesmon accounted for 78.2 ± 5.1% of immunoreactive caldesmon (150-kDa + 70-kDa); the fractional contents of a-smooth muscle actin, (3-nonmuscle, and y-

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Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct anti-atherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40–74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ul-trasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (−0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen-rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies which enforces a view that botanicals might represent promising drugs for anti-atherosclerotic therapy.

Atherosclerosis is characterized by inflammatory metabolic change with lipid accumulation in the artery. Atherosclerotic plaque occurs at discrete locations in the arterial system and involves the proliferation of smooth muscle cells (SMCs) together with imbalance of the extracellular matrix elements, elastic fiber in particular. The role of elastin in arterial development and disease was confirmed by generating mice that lack elastin. Thus, elastin is a critical regulatory molecule that regulates the pheno-typic modulation, proliferation and migration of SMCs. We estimated that elastin expression and SMC proliferation are coupled inversely: potent stimulators of cell proliferation may potentially inhibit elastin expression and potent inhibitors of cell proliferation can stimulate elastin expression. Moreover, elastin was found to be expressed maximally at the G0 and minimally at the G2/M phase during the cell cycle, suggesting that its expression is regulated by the cell growth state. The elastin peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin expression. The inhibition of elastin expression by elastin fragments may be reflected in the negative feedback regulatory mechanism. The relationship between cell proliferation and elastin expression may be changed in atherosclerosis. Areas of atherosclerotic plaque show abnormality of elasticity and permeability from the viewpoint of the physiological function of the arterial wall. The etiology was estimated to be that cholesterol and calcium are deposited on the elastic fiber, resulting in decreased elastin synthesis and cross-linking formation. In addition, these dysfunctions of elastin fiber are also associated, in that the down-regulation of elastin and its related components (fibrillin-1 and lysyl oxidase) are directly related to calcification in SMCs. The denatured arterial elastin by cholesterol and calcium accumulation was also susceptible to proteolytic enzymes such as elastase and matrix metalloproteinase (MMP). Therefore, metabolic change in elastic fiber induces decreased elasticity and is associated with essential hyper-tension. Vitamin K2 is used in drug therapy against atherosclerosis, or calcification in diabetes mellitus or dialysis, due to its promotion of the carboxylation of the matrix Gla protein. J Atheroscler Thromb, 2004; 11: 236-245. The heart and arteries are always active mechanically and seem to wear out more than any other system or organs. The potential energy accumulated in the stretching of the vessel wall during contraction of the heart (sys-tole) is dissipated in the elastic recoil of the wall during the period when the heart is inactive (diastole). This release of tension in the wall serves as an auxiliary pump, forcing the blood forward during diastole. Thus, near the heart, the flow of blood is intermittent and it is associated with the elasticity of the wall. The walls of the large conducting vessels make it possible to have a continuous flow with an intermittent pump. The normal human artery wall com...

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The double-blinded placebo-controlled randomized study has been performed in 51 coronary heart disease (CHD) patients to estimate the effects of time-released garlic powder tablets Allicor on the values of 10-year prognostic risk of acute myocardial infarction (fatal and non-fatal) and sudden death, with the respect of secondary CHD prevention. It has been demonstrated that 12-month treatment with Allicor results in the significant decrease of cardiovascular risk by 1.5-fold in men (p < 0.05), and by 1.3-fold in women. The above results were equitable also in terms of relative risks. The main effect that played a role in cardiovascular risk reduction was the decrease in LDL cholesterol by 32.9 mg/dl in men (p < 0.05), and by 27.3 mg/dl in women. Thus, the most significant effects were observed in men, while in women the decrease of cardiovascular risk appeared as a trend that might be due presumably to the insufficient sample size. Since Allicor is the remedy of natural origin, it is safe with the respect to adverse effects and allows even perpetual administration that may be crucial for the secondary prevention of atherosclerotic diseases in CHD patients.