PMID- 17414225 OWN - NLM STAT- MEDLINE DCOM- 20070508 LR - 20220408 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 49 IP - 3 DP - 2007 Mar TI - Anti-atherogenic effects of a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea phenolics in human aortic smooth muscle cells. PG - 140-5 AB - Certain drastic behavioral modifications by arterial wall smooth muscle cells (SMC) have been considered key steps in the formation of atherosclerotic lesions: massive migration of SMC from the media to the intima layer of the vessel, dedifferentiation of SMC to proliferating phenotype, and increased secretion of inflammatory cytokines as a response to inflammatory stimuli. We investigated the anti-atherogenic effects of naturally occurring compounds (ascorbic acid, green tea extract, lysine, proline, arginine, and N-acetyl cysteine) using the model of cultured aortic SMC. Cell growth was measured by DNA synthesis, cell invasiveness was measured through Matrigel, matrix metalloproteinase-2 (MMP-2) secretion was measured by zymography, and SMC secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) was measured by immunochemistry. Fetal bovine serum-stimulated SMC growth was inhibited by the nutrient mixture (NM) with 85% inhibition at 100 microg/mL. A corresponding concentration of epigallocatechin gallate (EGCG; 15 microM), the most active tea phenolic, produced a significant effect but one lower than NM. NM inhibited aortic SMC Matrigel invasion in a dose-dependent manner and significantly decreased MMP-2 expression. Stimulation of SMC with tumor necrosis factor-alpha significantly increased production and secretion of such mediators of inflammation as IL-6 and MCP-1; addition of 100 microg/mL NM inhibited secretion of MCP-1 and IL-6 by 65% and 47%, respectively. These data suggest that the NM of ascorbic acid, tea phenolics, and selected amino acids has potential in blocking the development of atherosclerotic lesions by inhibiting atherogenic responses of vascular SMC to pathologic stimuli and warrants in vivo studies. FAU - Ivanov, Vadim AU - Ivanov V AD - Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, California 95050, USA. FAU - Roomi, M Waheed AU - Roomi MW FAU - Kalinovsky, T AU - Kalinovsky T FAU - Niedzwiecki, Aleksandra AU - Niedzwiecki A FAU - Rath, Matthias AU - Rath M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Amino Acids) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (Phenols) RN - 0 (Plant Extracts) RN - 0 (Tea) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - PQ6CK8PD0R (Ascorbic Acid) SB - IM MH - Amino Acids/*pharmacology MH - Animals MH - Aorta/cytology/drug effects MH - Ascorbic Acid/*pharmacology MH - Atherosclerosis/*drug therapy/prevention & control MH - Catechin/analogs & derivatives/pharmacology MH - Cattle MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Chemokine CCL2/drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Humans MH - Immunochemistry MH - Interleukin-6/metabolism MH - Matrix Metalloproteinase 2/drug effects/metabolism MH - Myocytes, Smooth Muscle MH - Phenols/isolation & purification/pharmacology MH - Plant Extracts/*pharmacology MH - Tea/*chemistry EDAT- 2007/04/07 09:00 MHDA- 2007/05/09 09:00 CRDT- 2007/04/07 09:00 PHST- 2007/04/07 09:00 [pubmed] PHST- 2007/05/09 09:00 [medline] PHST- 2007/04/07 09:00 [entrez] AID - 00005344-200703000-00004 [pii] AID - 10.1097/FJC.0b013e3180308489 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2007 Mar;49(3):140-5. doi: 10.1097/FJC.0b013e3180308489.