Genomes and Genes
Inflammation and Injury in Obesity Hypertension in African American Adolescents
Principal Investigator: Bonita Falkner
Abstract: Hypertension is strongly associated with obesity. The current childhood obesity epidemic predicts rising rates of hypertension, diabetes, and cardiovascular diseases (CVD) with earlier onset and poorer outcomes especially among minority youth. The metabolic syndrome, a clinical construct that designates multiple CV risk factors within an individual, augments greatly the risk for CVD. The association of obesity with high BP and multiple CV risk factors is strong but not universal. Not all obese adults have the metabolic syndrome, nor do all obese adults develop hypertension, diabetes or early vascular disease. Our data on a cohort of African Americans, examined from adolescence into middle age, demonstrate the presence of the metabolic syndrome at a young age, with subsequent convergence of high BP with deterioration of glucose metabolism. Despite the high prevalence of obesity in this cohort, a substantial portion of obese participants have normal BP, glucose tolerance, and plasma lipids. Preliminary data on proteins secreted by adipose tissue in the obese with high BP (OHBP) and obese with normal BP (ONBP) indicate a pro-inflammatory profile in OHBP (lower adiponectin, higher interleukin 6, higher plasminogen activator inhibitor-1) compared to the reverse pattern in ONBP. Urinary albumin excretion (UAE), a marker of vascular injury is significantly higher in OHBP and correlates with interleukin-6 and adiponectin. In contrast to evidence of a pro-inflammatory adipokine profile and markers of vascular injury in OHBP, the ONBP sample had a favorable adipokine profile and absence of metabolic risk factors despite substantial obesity. DNA analyses detected genetic variants in candidate adipokine genes, indicating a genetic contribution to the favorable and unfavorable adipokine profile. Our overall hypothesis is: Evidence of vascular injury is detectable at a young age in obesity-high BP and is associated with a pro-inflammatory adipokine profile which, in turn, is associated with the presence of genetic variants in adipokine regulatory genes. A cross-sectional study on 300 African American adolescents is designed with the following aims: Determine;1) if OHBP is a high risk clinical phenotype for multiple CV risk factors;2) if OHBP is associated with a pro-inflammatory adipokine profile;and 3) if the OHBP phenotype has evidence of CV injury, ascertained by left ventricular mass index, peripheral vascular resistance, and UAE. The contribution of genetic variants in adipokine regulatory genes will be examined. Efficient methods are needed for detection and intervention to prevent premature CVD among the substantial numbers of children who already have multiple CV risk factors and possible target organ damage. The results to this study will contribute to improved capacity for identification of high risk minority youth as well as insights for development of novel therapies to abort and reverse early stages of CV vascular injury.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT
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Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
J Pediatr 162:94-100. 2013..To examine the relative effects of high blood pressure (HBP) and obesity on left ventricular mass (LVM) among African-American adolescents; and if metabolic or inflammatory factors contribute to LVM...
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Department of Pediatrics, Division of Pediatric Nephrology, University of Arkansas for Medical Sciences, Little Rock, USA
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Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
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Departments of Medicine SD, BF and Clinical Pharmacology and Experimental Therapeutics SWK, Thomas Jefferson University, Philadelphia, Pennsylvania and Nemours Cardiac Center SSG at A I DuPont Hospital for Children, Wilmington, Delaware
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Nemours Cardiac Center, Alfred I duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE, 19803, USA
Pediatr Cardiol 35:307-14. 2014..In African-American adolescents, BMI and SBP, but not inflammatory markers or adipokines, are important correlates of LA size and LVM. ..