Anti-atherosclerotic effects of garlic preparation in freeze injury model of atherosclerosis in cholesterol-fed rabbits.

BACKGROUND: Garlic (Allium sativum L.) is one of the most popular substances used to reduce various risks associated with cardiovascular disease. However, little is known on the direct effects of garlic on atherosclerosis. PURPOSE: In the present study we have examined the effect of per oral administration of the time-released garlic herbal preparation on serum atherogenicity and formation of intimal thickening after freeze injury in cholesterol-fed rabbits. METHODS: Group 1 rabbits maintained on the standard cholesterol-rich diet served as the control. Group 2 rabbits were fed the cholesterol-rich diet and treated with garlic preparation containing 300 mg garlic powder. RESULTS: Local thickening of the aortic media (i.e., the neointima formation) in the freeze injury zone was observed in all the rabbits. Regular garlic preparation therapy prevented the neointima formation and the accumulation of free and esterified cholesterol, triglycerides, phospholipids and collagen in the neointima, the effects being statistically significant. Garlic preparation also decreased serum lipid content by 1.5-fold and lowered atherogenic activity of blood serum (ability to induce lipid accumulation in cultured cells) induced by cholesterol-rich diet. CONCLUSION: The results obtained indicate that garlic preparation prevents the development of cholesterol-induced experimental atherosclerosis and possesses the direct anti-atherogenic activity.

Human adipose-tissue derived stromal cells in combination with hypoxia effectively support ex vivo expansion of cord blood haematopoietic progenitors.

The optimisation of haematopoietic stem and progenitor cell expansion is on demand in modern cell therapy. In this work, haematopoietic stem/progenitor cells (HSPCs) have been selected from unmanipulated cord blood mononuclear cells (cbMNCs) due to adhesion to human adipose-tissue derived stromal cells (ASCs) under standard (20%) and tissue-related (5%) oxygen. ASCs efficiently maintained viability and supported further HSPC expansion at 20% and 5% O2. During co-culture with ASCs, a new floating population of differently committed HSPCs (HSPCs-1) grew. This suspension was enriched with СD34+ cells up to 6 (20% O2) and 8 (5% O2) times. Functional analysis of HSPCs-1 revealed cobble-stone area forming cells (CAFCs) and lineage-restricted colony-forming cells (CFCs). The number of CFCs was 1.6 times higher at tissue-related O2, than in standard cultivation (20% O2). This increase was related to a rise in the number of multipotent precursors - BFU-E, CFU-GEMM and CFU-GM. These changes were at least partly ensured by the increased concentration of MCP-1 and IL-8 at 5% O2. In summary, our data demonstrated that human ASCs enables the selection of functionally active HSPCs from unfractionated cbMNCs, the further expansion of which without exogenous cytokines provides enrichment with CD34+ cells. ASCs efficiently support the viability and proliferation of cord blood haematopoietic progenitors of different commitment at standard and tissue-related O2 levels at the expense of direct and paracrine cell-to-cell interactions.

Lipid regulators during atherogenesis: expression of LXR, PPAR, and SREBP mRNA in the human aorta.

Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXRα, LXRß, PPARα, PPARγ, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression.

Correlation between lipid deposition, immune-inflammatory cell content and MHC class II expression in diffuse intimal thickening of the human aorta.

Inflammatory reactions driven by an accumulation in the intima of immune-inflammatory cells and focal lipid depositions are the hallmarks of atherogenesis. It is commonly accepted that immune-inflammatory cell accumulation and lipid deposition are associated with the very earlier stage of atherosclerosis but no study has yet focused on the determination of quantitative values of this association. The present study examined correlations between lipid deposition, immune-inflammatory cell content and major histocompatibility complex (MHC) class II molecule HLA-DR expression in diffuse intimal thickening (DIT), which is thought to represent the earliest macroscopic manifestation of atherosclerosis. In parallel consecutive tissue sections of DIT, lipids were examined by chromatographic analysis (including triglycerides, cholesteryl esters, free cholesterol and phospholipids), histochemically, using Oil Red O staining, and by electron microscopy. Immune-inflammatory cells and HLA-DR expression were examined immunohistochemically in consecutive sections of the same tissue specimens. The study revealed that lipids exhibited a non-uniform distribution throughout the intima. In the juxtaluminal sublayer, lipids were localized both intracellularly and extracellularly, whereas in the juxtamedial musculoelastic sublayer, lipids were present predominantly along elastic fibers. Lipid deposits were found to positively correlate with HLA-DR expression (r=0.79; p<0.001). The study also identified a positive correlation between lipid deposition and immune-inflammatory cell content but the correlation values varied between different sublayers of the tunica intima. The correlation between lipid deposition and immune-inflammatory cell content in the juxtaluminal sublayer of the intima was notably stronger (r=0.69; p<0.001) than in the juxtamedial musculoelastic layer (r=0.28; p<0.001). The findings of the present study support a view that lipid accumulation in the intima plays a role in the initiation of inflammatory reaction and that at the pre-lesional stage in the development of atherosclerosis, lipid-associated immune cell activation might occur primarily in the juxtaluminal portion of the intima.

Time-released garlic powder tablets lower systolic and diastolic blood pressure in men with mild and moderate arterial hypertension.

Numerous clinical investigations that have focused on the hypotensive effects of garlic-based preparations have led to controversial results that may be partially because of differences in the composition of the preparations and in the biological responses they induce. It is possible that garlic powder tablets with a prolonged mode of action could induce more potent biological effects. In this double-blind, placebo-controlled trial with an active control arm, the hypotensive action of time-released garlic powder tablets (Allicor) was compared with that of regular garlic pills (Kwai) in 84 men with mild or moderate arterial hypertension. After an 8-week placebo treatment run-in phase, patients were randomized either to 600 mg Allicor (n=30) or to placebo (n=20) daily for 8 weeks. In addition, in the open-label branch, patients received either 2400 mg Allicor daily (n=18) or 900 mg Kwai daily (n=16). Allicor treatment (600 mg daily) resulted in a reduction of both systolic and diastolic blood pressures by 7.0 mm Hg (95% confidence interval (95% CI): 5.3-8.7) and 3.8 mm Hg (95% CI: 2.7-4.8), respectively. Increasing the Allicor dosage to 2400 mg daily did not provide any additional benefit. Treatment with Kwai resulted in the same decrease in systolic blood pressure (5.4 mm Hg, 95% CI: 1.9-8.8) as that seen with Allicor, but no decrease in diastolic blood pressure was observed with Kwai. Different effects of Allicor and Kwai on diastolic blood pressure may be because of the prolonged action of Allicor, which allows better bioavailability of the vasoactive constituents of garlic powder. The results of this study show that time-released garlic powder tablets are more effective for the treatment of mild and moderate arterial hypertension than are regular garlic supplements.

Lipid-lowering effects of time-released garlic powder tablets in double-blinded placebo-controlled randomized study.

AIM: Clinical investigations of the effects of garlic preparations in hypercholesterolemia have demonstrated somewhat controversial results. These discrepancies may be due to the differences of the composition of garlic preparations and the biological response they may induce. The study was undertaken to test the hypothesis that garlic powder tablets with a prolonged mode of action promise potent biological effects. METHODS: The lipid-lowering effects of time-released garlic powder tablets, Allicor (600 mg daily), were investigated in a double-blinded placebo-controlled randomized study in 42 men aged 35-70 with mild hypercholesterolemia. RESULTS: Allicor treatment resulted in a moderate but statistically significant decrease in total cholesterol level that was observed after 8 and 12 weeks of active treatment. By the end of the study, total cholesterol in Allicor-treated patients had fallen by 7.6% (p=0.004) as compared to the level at randomization, and was 11.5% lower than the placebo group (p=0.005). LDL cholesterol in Allicor-treated patients fell by 11.8% (p=0.002) and 13.8% (p=0.009), respectively. HDL cholesterol also increased significantly after 8 and 12 weeks of treatment. By the end of the study, HDL cholesterol in Allicor-treated patients had increased by 11.5% (p=0.013). CONCLUSION: The obtained results are in good agreement with trials that have demonstrated the cardioprotective action of garlic preparations and may be due to the use of a time-released form of garlic powder tablets that provides a prolonged biological effect.