The emerging role of plasma lipidomics in cardiovascular drug discovery
Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland, OH, USA. Expert Opinion on Drug Discovery
(Impact Factor: 3.54).
01/2012; 7(1):63-72. DOI: 10.1517/17460441.2012.644041
INTRODUCTION: With the rising global incidence of cardiovascular disease, the challenge for the pharmaceutical industry is to identify novel biomarkers that will allow not only for the development of the next generation of cardiometabolic therapeutics, but also to serve as a sensitive mechanism to monitor and predict drug efficacy and potential toxicity. The advent of an 'omics' (systems biological) approach has vast implications for future disease treatment and prevention. Lipidomics is the latest addition to the 'omics' family and is rapidly gaining attention due to the technological improvements in mass spectrometry, allowing for the characterization of large number of lipids (and their respective subclasses) in a short amount of time with relatively minimal preparation. AREAS COVERED: The authors discuss the various techniques involved in plasma lipidomics as well as outline the role that lipidomics will play in phenotyping disease processes and corresponding therapeutic strategies. The article was formed through comprehensive Medline search of relevant publications in this area. EXPERT OPINION: Despite the wealth of data that will emerge regarding the various lipid-molecular interactions and the functions of lipids within cells, a major challenge will be the parallel emergence of novel bioinformatics platforms in order to integrate this enormous data set with information generated from the emerging fields of genomics and proteomic analysis. Despite these challenges, lipidomics is likely to result in the reclassification of diseases from a molecular perspective and play a key role the eventuation of personalized medicine.
Available from: Frode Norheim
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ABSTRACT: In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases.
Nutrients 12/2012; 4(12):1898-944. DOI:10.3390/nu4121898 · 3.27 Impact Factor
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ABSTRACT: Mood disorders such as major depressive disorder and bipolar disorder-and their consequent effects on the individual and society-are among the most disabling and costly of all medical illnesses. Although a number of antidepressant treatments are available in clinical practice, many patients still undergo multiple and lengthy medication trials before experiencing relief of symptoms. Therefore a tremendous need exists to improve current treatment options and to facilitate more rapid, successful treatment in patients suffering from the deleterious neurobiological effects of ongoing depression. Toward that end, ongoing research is exploring the identification of biomarkers that might be involved in prevention, diagnosis, treatment response, severity, or prognosis of depression. Biomarkers evaluating treatment response will be the focus of this review, given the importance of providing relief to patients in a more expedient and systematic manner. A novel approach to developing such biomarkers of response would incorporate interventions with a rapid onset of action-such as sleep deprivation or intravenous drugs (e.g., ketamine or scopolamine). This alternative translational model for new treatments in psychiatry would facilitate shorter studies, improve feasibility, and increase higher compound throughput testing for these devastating disorders.
Biological psychiatry 01/2013; 73(12). DOI:10.1016/j.biopsych.2012.11.031 · 10.26 Impact Factor
Available from: Joanne E Curran
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ABSTRACT: Both as a component of metabolic syndrome and as an independent entity, hypertension poses a continued challenge with regard to its diagnosis, pathogenesis, and treatment. Previous studies have documented connections between hypertension and indicators of lipid metabolism. Novel technologies, such as plasma lipidomic profiling, promise a better understanding of disorders in which there is a derangement of the lipid metabolism. However, association of plasma lipidomic profiles with hypertension in a high-risk population, such as Mexican Americans, has not been evaluated before. Using the rich data and sample resource from the ongoing San Antonio Family Heart Study, we conducted plasma lipidomic profiling by combining high-performance liquid chromatography with tandem mass spectroscopy to characterize 319 lipid species in 1192 individuals from 42 large and extended Mexican American families. Robust statistical analyses using polygenic regression models, liability threshold models, and bivariate trait analyses implemented in the SOLAR software were conducted after accounting for obesity, insulin resistance, and relative abundance of various lipoprotein fractions. Diacylglycerols, in general, and the DG 16:0/22:5 and DG 16:0/22:6 lipid species, in particular, were significantly associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), as well as liability of incident hypertension measured during 7140.17 person-years of follow-up. Four lipid species, including the DG 16:0/22:5 and DG 16:0/22:6 species, showed significant genetic correlations with the liability of hypertension in bivariate trait analyses. Our results demonstrate the value of plasma lipidomic profiling in the context of hypertension and identify disturbance of diacylglycerol metabolism as an independent biomarker of hypertension.
Hypertension 06/2013; 62(3). DOI:10.1161/HYPERTENSIONAHA.113.01396 · 6.48 Impact Factor
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