Non-pharmacological control of atherosclerosis
Principal Investigator: Sampath Parthasarathy
Abstract: DESCRIPTION (provided by applicant): Inflammatory nature of atherosclerosis and the vulnerability of the plaque have suggested the need to identify agents that would inhibit these processes in the treatment of the disease. We recently observed that the administration of sesame oil to atherosclerotic mice not only reduced the blood lipids by 50% but also prevented atherosclerosis by over 85%. Preliminary results indicated that sesame oil inhibited the expression of pro-inflammatory genes and genes related to plaque vulnerability while it enhanced the expression of genes involved in reverse cholesterol transport. There are two potential possibilities-.-these effects are due hitherto unknown effects of the fatty acid constituents of sesame oil (It contains almost equal amounts of mono and polyunsaturated fatty acids), or due to its unusual non-saponifiable components. The results also posed an important question, whether lowering of plasma lipids themselves resulted in the decrease of inflammation and promoted plaque stability and increased reverse cholesterol transport or the gene effects of sesame oil or its constituents were responsible for the observed decrease in lipids and atherosclerosis. Sesame oil contains equal amounts of mono- and poly unsaturated fatty acids and contains bio-active non-saponifiable components that are potent antioxidants and PPAR1 agonists. The overall goal of the study is to determine the mechanisms by which fatty acid components and non- saponifiable components of sesame oil could exert beneficial in atherosclerosis. In lieu of vitamin E's failure in protecting human atherosclerosis, identification of the mechanisms by which the non-saponifiable components of sesame oil might complement the anti-atherosclerotic effects of dietary unsaturated fat could lead to major new pharmacological alternatives and directions. The Goals of the proposed studies are: 1. To compare the efficacy of sesame oil with sunflower oil in its anti-atherosclerotic effects with using LDL receptor knockout animals and to delineate and identify the anti-atherosclerotic effects of its non- saponifiable components. 2. Identify the anti-atherosclerotic genes that are regulated by sesame oil and its saponifiable and non- saponifiable components and to define potential molecular mechanisms that may be involved in their action. 3. To determine whether sesame oil supplementation decrease markers of cardiovascular risk in normal and high risk human subjects. Implications: Dietary prevention of atherosclerosis has major advantages to pharmacological control, being inexpensive, sensible, and healthy. The proposed study could lead to the identification of components that could be "cheap" alternatives to expensive medication offering valuable "adjunct therapy" to existing medications, It would also lead to new class of drug development.
Funding Period: 2010-07-01 - 2015-05-31
more information: NIH RePORT
- Effects of a novel pharmacologic inhibitor of myeloperoxidase in a mouse atherosclerosis modelCuiqing Liu
Department of Physiology, Hangzhou Normal University, Hangzhou, China
PLoS ONE 7:e50767. 2012..These findings demonstrate a role for pharmacologic modulation of myeloperoxidase in atherosclerosis...
- The Center for Native and Pacific Health Disparities ResearchMARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013..5) To prepare and empower our diverse Native and Pacific People communities to take ownership of their own health and wellness. ..
- GENE THERAPY FOR HEMOPHILIAKatherine A High; Fiscal Year: 2013..The projects are highly interactive, and all three take full advantage of the proposed cores. ..
- MULTIDISCIPLINARY STRUCTURES AT VASCULAR CELL SURFACESTimothy A Springer; Fiscal Year: 2013..Administrative (Springer) and Protein Expression (Lu) Cores enhance efficiency of the PPG. (End of Abstract) ..
- T-cell Co-stimulation in Obesity-induced Inflammation and AtherosclerosisVince N Montes; Fiscal Year: 2013..The research environment at the University of Washington is excellent for a budding physician- scientist, and I plan on taking absolute advantage of the resources available. (End of Abstract) ..
- Endothelial Cell Phenotypes in Health and DiseaseWilliam C Aird; Fiscal Year: 2013..Core C ("Gene Targeting Core";William C. Aird, Core Leader) provides the necessary tools for targeting the Hprt locus and the loci of endogenous genes in ES cells and mice. ..
- Formation of Omega 3-Derived Electrophiles During InflammationFRANCISCO JOSE SCHOPFER; Fiscal Year: 2013..It is expected that this proposal will lead to a better understanding of w-3 fatty acid effects and to improved pharmacological approaches to decrease atherosclerosis and its detrimental effects. ..
- Mechanisms for Dysfunctional HDL Formation in Familial HypercholesterolemiaMacrae F Linton; Fiscal Year: 2013..Our results may lead to the development of new markers of HDL function, provide new pharmacologic targets for improving HDL function, and identify HDL as a target of therapy in FH patients. ..
- Oxidation Hypothesis Revisited: Haptoglobin Genotype &Diabetic AtherosclerosisANDREW PETER LEVY; Fiscal Year: 2013..abstract_text> ..
- INNATE AND ADAPTIVE IMMUNE RESPONSES IN TH2-HIGH ASTHMAJohn V Fahy; Fiscal Year: 2013..Including studies in human biospecimens in a PPG that promises to advance understanding of airway TH2 inflammation in ways that are highly relevant to patients with asthma. ..
- Thrombus Formation and Antithrombotic InterventionJohn H Griffin; Fiscal Year: 2013..New knowledge will contribute to improving prevention, diagnosis and treatment of relevant diseases related to thrombosis. ..
- INTEGRATED MECHANISMS OF CARDIAC MALADAPTATIONR John Solaro; Fiscal Year: 2013..Studies proposed here offer the potential for novel diagnostic procedures early in the progression of the disorders, and targets for novel therapies. (End of Abstract) ..
- Mechanisms of Microvascular Control and Coordination in Health and DiseaseGerald A Meininger; Fiscal Year: 2013..End of Abstract) ..
- The Metabolic Impact of Congenital Heterozygous ApoC-III Deficiency in HumansTONI ILANA POLLIN; Fiscal Year: 2013..This project will look more closely at the effects of the deficiency on human metabolism to better understand the function of the apoC-III protein and its potential as a drug target. ..
- Subtype Specific LXR Activity Limits AtherosclerosisIra G Schulman; Fiscal Year: 2013..The results of these studies should provide innovative strategies for the development of therapies for the treatment of cardiovascular disease. ..
- Modulation of atherosclerosis by cannabinoid type 2 receptorDouglas P Thewke; Fiscal Year: 2013....
- GPCR Signaling Through a Novel NF-kB PathwayLinda M McAllister-Lucas; Fiscal Year: 2013..We anticipate that the results will broadly inform development of pharmaceutical strategies for curtailing the contributions of inflammation to atherogenesis. ..
- Control of Sterol and Lipoprotein Homeostasis by miRNAAngel Baldán; Fiscal Year: 2013..The results of these studies might lead to novel, improved ways to manage patients with hypercholesterolemia and/or patients with cholestasis. ! ..
- Resveratrol as an Innovative Cardiovascular Therapeutic Strategy in LupusAllison B Reiss; Fiscal Year: 2013..To validate our hypothesis that resveratrol impedes development of atherosclerosis via effects on cholesterol flux in the vessel wall, we will examine the vasculature in vivo in this animal model prior to consideration of human testing. ..
- LIPID AND LIPOPROTEIN METABOLISM IN ATHEROSCLEROSISAlan M Fogelman; Fiscal Year: 2013..These six Projects will be supported by four cores and together will form a highly interactive and synergistic Program Project that is focused on lipid and lipoprotein metabolism in atherosclerosis. ..
- Avoiding toxicity associated with MTP ablationM Mahmood Hussain; Fiscal Year: 2013..Proposed studies may lead to new therapeutic modalities for the treatment of various disorders associated with high plasma lipids. ..
- Inflammatory responses of vascular cellsPaul L Fox; Fiscal Year: 2013..abstract_text> ..
- MicroRNAs as physiological and pathological regulators of cholesterol homeostasisKathryn J Moore; Fiscal Year: 2013..These studies may uncover novel therapeutic strategies for the treatment of cardiovascular disease. ..
- Neurohumoral control of veins in hypertensionGregory D Fink; Fiscal Year: 2013..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
- Prevention of age-associated musculoskeletal loss by n-3 fatty acidsMd Mizanur Rahman; Fiscal Year: 2013..abstract_text> ..