John F Keaney

University of Massachusetts Medical School, Worcester, Massachusetts, United States

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Publications (135)1231.47 Total impact

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    ABSTRACT: MicroRNAs (miRNAs) are associated with cardiovascular disease (CVD), control gene expression, and are detectable in the circulation.
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2014; · 4.56 Impact Factor
  • New England Journal of Medicine 05/2014; 370(20):1957. · 54.42 Impact Factor
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    ABSTRACT: Whereas endogenous carbon monoxide (CO) is cytoprotective at physiologic levels, excess CO concentrations are associated with cardiometabolic risk and may represent an important marker of progression from subclinical to clinical cardiovascular disease (CVD). In 1926 participants of the Framingham Offspring Study (aged 57 ± 10 years, 46% women), we investigated the relationship of exhaled CO, a surrogate of blood CO concentration, with both prevalent subclinical CVD and incident clinical CVD events. Presence of subclinical CVD was determined using a comprehensive panel of diagnostic tests used to assess cardiac and vascular structure and function. Individuals with the highest (>5 p.p.m.) compared with lowest (≤4 p.p.m.) CO exposure were more likely to have subclinical CVD [odds ratios (OR): 1.67, 95% CI: 1.32-2.12; P < 0.001]. During the follow-up period (mean 5 ± 3 years), 193 individuals developed overt CVD. Individuals with both high CO levels and any baseline subclinical CVD developed overt CVD at an almost four-fold higher rate compared with those with low CO levels and no subclinical disease (22.1 vs. 6.3%). Notably, elevated CO was associated with incident CVD in the presence [hazards ration (HR): 1.83, 95% CI: 1.08-3.11; P = 0.026] but not in the absence (HR: 0.80, 95% CI: 0.42-1.53; P = 0.51) of subclinical CVD (Pinteraction = 0.019). Similarly, subclinical CVD was associated with incident CVD in the presence of high but not low CO exposure. Our findings in a community-based sample suggest that elevated CO is a marker of greater subclinical CVD burden and, furthermore, a potential key component in the progression from subclinical to clinical CVD.
    European Heart Journal 02/2014; · 14.72 Impact Factor
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    ABSTRACT: Sirtuin 3 (SIRT3), an important regulator of energy metabolism and lipid oxidation, is induced in fasted liver mitochondria and implicated in metabolic syndrome. In fasted liver, SIRT3-mediated increases in substrate flux depend on oxidative phosphorylation (OXPHOS), but precisely how OXPHOS meets the challenge of increased substrate oxidation in fasted liver remains unclear. Here, we show that liver mitochondria in fasting mice adapt to the demand of increased substrate oxidation by increasing their OXPHOS efficiency. In response to cAMP signaling, SIRT3 deacetylated and activated leucine-rich protein 130 (LRP130; official symbol, LRPPRC), promoting a mitochondrial transcriptional program that enhanced hepatic OXPHOS. Using mass spectrometry, we identified SIRT3-regulated lysine residues in LRP130 that generated a lysine-to-arginine (KR) mutant of LRP130 that mimics deacetylated protein. Compared with wild-type LRP130 protein, expression of the KR mutant increased mitochondrial transcription and OXPHOS in vitro. Indeed, even when SIRT3 activity was abolished, activation of mitochondrial transcription and OXPHOS by the KR mutant remained robust, further highlighting the contribution of LRP130 deacetylation to increased OXPHOS in fasted liver. These data establish a link between nutrient sensing and mitochondrial transcription that regulates OXPHOS in fasted liver and may explain how fasted liver adapts to increased substrate oxidation.
    The Journal of clinical investigation 01/2014; · 15.39 Impact Factor
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    ABSTRACT: On November 12, 2013, updated guidelines for the treatment of high blood cholesterol levels were released by the American College of Cardiology-American Heart Association (ACC-AHA) Task Force on Practice Guidelines.(1) This update represents the first major guideline revision since the National Cholesterol Education Program released its Adult Treatment Panel III report in 2002.(2) The previous guidelines were widely accepted and applied with relative consistency. In contrast, the new guidelines have already been the subject of controversy, with some observers arguing that some elements of the recommendations are not evidence-based.(3) Nevertheless, these recommendations may have a major effect on the clinical . . .
    New England Journal of Medicine 11/2013; · 54.42 Impact Factor
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    ABSTRACT: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia. Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood was obtained from arterial blood samples at the time of cardiac catheterization and cell-specific miRNA profiling was performed. Expression of 343 miRNAs was quantified from whole blood, plasma, platelets, and peripheral blood mononuclear cells using a high-throughput, quantitative Real-Time polymerase-chain reaction system (qRT-PCR). MiRNAs associated with STEMI as compared to NSTEMI patients included miR-25-3p, miR-221-3p, and miR-374b-5p. MiRNA 30d-5p was associated with plasma, platelets, and leukocytes in both STEMI and NSTEMI patients; miRNAs 221-3p and 483-5p were correlated with plasma and platelets only in NSTEMI patients. Cell-specific miRNA profiles differed between patients with STEMI and NSTEMI. The miRNA distribution is also unique amongst plasma, platelets, and leukocytes in patients with ischemic heart disease or ACS. Our findings suggest unique miRNA profiles among the circulating subcomponents in patients presenting with myocardial ischemia.
    Family medicine & medical science research. 10/2013; 2(2):108.
  • John F Keaney
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    ABSTRACT: Acute coronary syndrome is an umbrella term that is used to describe the abrupt reduction of blood flow to myocardial tissue, typically associated with the rupture of a coronary atherosclerotic plaque. Rupture exposes the blood to plaque contents, resulting in the deposition and activation of platelets and the formation of thrombi. Complete thrombotic occlusion produces ST-segment elevation myocardial infarction, whereas incomplete impairment of coronary blood flow results in unstable angina or, when biomarkers for myocardial injury are present, non-ST-segment elevation myocardial infarction (NSTEMI). Because the rupture of a plaque incites platelet activation and thrombosis, treatments for unstable angina and NSTEMI . . .
    New England Journal of Medicine 09/2013; · 54.42 Impact Factor
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    ABSTRACT: Cardiovascular disease is a complex disorder influenced by interactions of genetic variants with environmental factors. However, there is no information from large community-based studies examining the relationship of circulating cell-specific RNA to inflammatory proteins. In light of the associations among inflammatory biomarkers, obesity, platelet function, and cardiovascular disease, we sought to examine the relationships of C-reactive protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory transcripts in platelets. We quantified circulating levels of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS) Offspring cohort examination 8 (mean age, 66.6±6.6 years; 46% men). We measured the expression of 15 relevant genes by high-throughput quantitative reverse transcriptase polymerase chain reaction from platelet-derived RNA and used multivariable regression to relate serum concentrations of CRP and IL-6 with gene expression. Levels of CRP and IL-6 were associated with 10 of the 15 platelet-derived inflammatory transcripts, ALOX5, CRP, IFIT1, IL6, PTGER2, S100A9, SELENBP1, TLR2, TLR4, and TNFRSF1B (P<0.001). Associations between platelet mRNA expression with CRP and IL-6 persisted after multivariable adjustment for potentially confounding factors. Six genes positively associated with CRP and IL-6 in the FHS sample were also upregulated in megakaryocytes in response to CRP and IL-6 exposure. Our data highlight the strong connection between the circulating inflammatory biomarkers CRP and IL-6 and platelet gene expression, adjusting for cardiovascular disease risk factors. Our results also suggest that body weight may directly influence these associations.
    Arteriosclerosis Thrombosis and Vascular Biology 08/2013; · 6.34 Impact Factor
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    ABSTRACT: Rationale: Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. Objective: To determine how mitochondria impact endothelial cell function. Methods and Results: We report here that stimuli for endothelial cell proliferation evoke strong upregulation of mitochondrial uncoupling protein 2 (UCP2). Analysis in silico indicated increased UCP2 expression is common in highly proliferative cell types, including cancer cells. Upregulation of UCP2 was critical for controlling mitochondrial membrane potential (Δψ) and superoxide production. In the absence of UCP2, endothelial growth stimulation provoked mitochondrial network fragmentation and premature senescence via a mechanism involving superoxide-mediated p53 activation. Mitochondrial network fragmentation was both necessary and sufficient for the impact of UCP2 on endothelial cell phenotype. Conclusions: These data identify a novel mechanism whereby mitochondria preserve normal network integrity and impact cell phenotype via dynamic regulation of UCP2.
    Circulation Research 07/2013; · 11.86 Impact Factor
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    ABSTRACT: OBJECTIVE: Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. APPROACH AND RESULTS: We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61±9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. CONCLUSIONS: Of 11 biomarkers, TNFRII was associated nominally with incident major CVD, and significantly with all-cause mortality, which renders it an interesting target for future research. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2013; · 6.34 Impact Factor
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    ABSTRACT: OBJECTIVES: Traditional clinical risk factors are associated with inflammation cross-sectionally, but associations of longitudinal variation in inflammatory biomarkers with corresponding changes in clinical risk factors are incompletely described. We sought to analyze clinical factors associated with change in inflammation in the community. METHODS: We studied 3013 Framingham Offspring (n = 2735) and Omni Cohort (n = 278) participants (mean age 59 years, 55% women, 9% ethnic/racial minority) who attended two consecutive examination cycles (mean 6.7 years apart). We selected ten inflammatory biomarkers representing distinctive biological functions: C-reactive protein (CRP), intercellular adhesion molecule-1, interleukin-6, isoprostanes, lipoprotein-associated phospholipase-2 (Lp-PLA2) activity, Lp-PLA2-mass, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II (TNFRII). We constructed multivariable-adjusted regression models to assess the relations of baseline, follow-up and change in clinical risk factors with change in biomarker concentrations over time. RESULTS: Baseline, follow-up and change in clinical risk factors explain a moderate amount of the variation in biomarker concentrations across 2 consecutive examinations (ranging from r(2) = 0.28 [TNFRII] up to 0.52 [Lp-PLA2-mass]). In multivariable models, increasing body-mass index, smoking initiation, worsening lipid profile, and increasing waist size were associated with increasing concentrations of several biomarkers. Conversely, hypercholesterolemia therapy and hormone replacement cessation were associated with decreasing concentrations of biomarkers such as CRP, Lp-PLA2-mass and activity. CONCLUSION: Cardiovascular risk factors have different patterns of association with longitudinal change in inflammatory biomarkers and explain modest amounts of variability in biomarker concentrations. Nevertheless, a substantial proportion of longitudinal change in inflammatory markers is not explained by traditional risk factors.
    Atherosclerosis 02/2013; · 3.71 Impact Factor
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    ABSTRACT: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P-selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age- and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors.
    Journal of the American Heart Association. 01/2013; 2(6):e000307.
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    ABSTRACT: Sleep disordered breathing is associated with cardiovascular disease. The pathophysiologic mechanisms remain unclear, but enhanced vascular inflammation is implicated. We sought to evaluate the association of sleep disordered breathing with biomarkers of inflammation. Cross-sectional, observational. Community-based. There were 900 participants from the Framingham Heart Study site of the Sleep Heart Health Study (52% females, mean age 60 y, 23% ethnic minorities). None. We assessed circulating levels of nine inflammatory biomarkers in relation to polysomnographically-derived apnea-hypopnea index and hypoxemia index (% sleep time with oxyhemoglobin saturation < 90%). Multivariable models were adjusted for demographics, smoking, cardiovascular diseases, diabetes, and other potential confounders, without and with adjustment for body mass index. With multivariable adjustment not including body mass index, the apnea-hypopnea index was associated with C-reactive protein, inter-leukin-6, fibrinogen, intercellular adhesion molecule-1, and P-selectin levels and hypoxemia index was associated with C-reactive protein, interleukin-6, and fibrinogen levels. After adjustment for body mass index, only the association of interleukin-6 with sleep disordered breathing remained significant: the adjusted mean serum interleukin-6 level was 2.93, 3.14, 3.34, and 4.62 pg/mL, respectively, in participants with apnea-hypopnea index < 5, 5-14.9, 15-29.9, and ≥ 30 events/h (P = 0.01 for trend) and 2.97, 3.01, 3.35, and 4.85 pg/mL, respectively, in participants with hypoxemia index < 0.5, 0.5-4.9, 5-9.9, and ≥ 10% of sleep time (P = 0.02 for trend). In a community-based sample, sleep disordered breathing is associated with higher levels of interleukin-6, a marker of myocardial infarction risk and mortality. Adiposity may mediate the increased levels of C-reactive protein, fibrinogen, intercellular adhesion molecule-1, and P-selectin observed in sleep disordered breathing. CITATION: Chami HA; Fontes JD; Vasan RS; Keaney JF; O'Connor GT; Larson MG; Benjamin EJ; Gottlieb DJ. Vascular Inflammation and sleep disordered breathing in a community-based cohort. SLEEP 2013;36(5):763-768.
    Sleep 01/2013; 36(5):763-8. · 5.10 Impact Factor
  • Kai Chen, John F Keaney
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    ABSTRACT: Cardiovascular disease (CVD) continues to be a substantial health-care burden, despite recent treatment advances. Oxidative stress has long been regarded as a key pathophysiological mediator that ultimately leads to CVD including atherosclerosis, hypertension and heart failure. Over the past decade, emerging evidence has shifted our understanding of reactive oxygen species (ROS) from its harmful role to being signaling molecules. Here, we reviewed recent advances in our understanding of ROS that mediate the complex process of CVDs, with a focus on major ROS signaling and sources such as mitochondria and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidases.
    Current Atherosclerosis Reports 10/2012; 14(5):476-83. · 2.92 Impact Factor
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    ABSTRACT: Context: Fetuin-A, retinol-binding protein 4 (RBP4), and fatty-acid binding protein 4 (FABP4) are novel biomarkers that may link adiposity to insulin resistance and the metabolic syndrome (MetSyn). Objective: The aim of this study was to investigate the correlates of these three adiposity biomarkers in a large community-based sample. Design, Setting, Participants, and Outcomes: Serum concentrations of fetuin-A, RBP4, and FABP4 were assayed in 3658 participants of the Third Generation Framingham Heart Study cohort (mean age 40 yr, 54% women). We used multivariable regression to cross-sectionally relate biomarkers to insulin resistance, cardiovascular risk factors, and the MetSyn. The genetic contribution to inter-individual variation in biomarker levels was assessed using variance-components analysis. Results: All three biomarkers exhibited sexual dimorphisms (levels higher in women for fetuin-A and FABP4 but greater in men for RBP4) and were associated positively with insulin resistance assessed using the homeostasis model, with high-sensitivity C-reactive protein, and with prevalent MetSyn (P < 0.01 for all). The biomarkers showed distinct patterns of association with metabolic risk factors. RBP4 levels were correlated with body mass index only in unadjusted but not in adjusted models. None of the biomarkers were associated with prevalent diabetes in multivariable models. Circulating fetuin-A, RBP4, and FABP4 levels showed modest heritability, ranging from 15-44% (all P < 0.0001). Conclusions: In our large young- to middle-aged community-based sample, we observed that circulating levels of fetuin-A, RBP4, and FABP4 are associated with insulin resistance and with distinct components of MetSyn consistent with the multifactorial pathogenesis of metabolic dysregulation.
    The Journal of Clinical Endocrinology and Metabolism 08/2012; 97(10):E1943-7. · 6.31 Impact Factor
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    ABSTRACT: We investigated whether AMP-activated protein kinase (AMPK) may be involved in the signaling processes leading to exercise-mediated vascular protection. The effects of voluntary exercise on AMPK activity, endothelial NO synthase expression and phosphorylation, vascular reactive oxygen species formation, and cell senescence were tested in α1AMPK knockout and corresponding wild-type mice. Exercise significantly improved endothelial function, and increased plasma nitrite production in wild-type mice, associated with an activation of aortic AMPK assessed by its phosphorylation at threonine 172. In addition, regular physical activity resulted in an upregulation of endothelial NO synthase protein, serine 1177 endothelial NO synthase phosphorylation, and an increase of circulating Tie-2(+)Sca-1(+)Flk-1(+) myeloid progenitor cells. All these changes were absent after α1AMPK deletion. In addition, exercise increased the expression of important regulators of the antioxidative defense including heme oxygenase-1 and peroxisome proliferator-activated receptor γ coactivator 1α, decreased aortic reactive oxygen species levels, and prevented endothelial cell senescence in an α1AMPK-dependent manner. Intact α1AMPK signaling is required for the signaling events leading to the manifestation of vascular protective effects during exercise. Pharmacological AMPK activation might be a novel approach in the near future to simulate the beneficial vascular effects of physical activity.
    Arteriosclerosis Thrombosis and Vascular Biology 04/2012; 32(7):1632-41. · 6.34 Impact Factor
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    ABSTRACT: Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy. In experimental studies, activation of the inflammatory regulator, nuclear factor kappa B (NFlB), contributes to endothelial activation and reduced nitric oxide production. We treated patients with coronary artery disease with sulfasalazine, an inhibitor of NFκB, and placebo in a randomized, double-blind, crossover study design. Brachial artery flow-mediated dilation (FMD) and digital vascular function were measured at baseline and after each 6-week treatment period. Of the 53 patients enrolled in the crossover study, 32 (age 60 ± 10, 22% female) completed all the visits, with a high rate of study withdrawal due to gastrointestinal side effects. In a subset of 10 participants, we compared the effects of 4 days of sulfasalazine treatment (n = 5) to no treatment (n = 5) on NFκB-regulated gene expression in peripheral blood mononuclear cells. Tumor necrosis factor α-stimulated expression of CD69 and NFlB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment. However, FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment. Short-term sulfasalazine inhibited NFlB activity; however, long-term treatment was poorly tolerated and did not improve endothelial function. Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease. Further studies are warranted to investigate the potential for NFlB inhibition to reduce cardiovascular risk.
    Vascular Medicine 04/2012; 17(2):101-7. · 1.62 Impact Factor
  • Koichi Sugamura, John F Keaney
    Nature medicine 01/2012; 18(6):856-8. · 27.14 Impact Factor
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    ABSTRACT: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.
    European Heart Journal 01/2012; 33(2):238-51. · 14.72 Impact Factor
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    John F Keaney
    Circulation 11/2011; 124(22):e559-60. · 15.20 Impact Factor

Publication Stats

8k Citations
1,231.47 Total Impact Points

Institutions

  • 2008–2014
    • University of Massachusetts Medical School
      • • Department of Medicine
      • • Division of Cardiovascular
      Worcester, Massachusetts, United States
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • Tufts University
      Georgia, United States
    • Harvard University
      Cambridge, Massachusetts, United States
    • Johannes Gutenberg-Universität Mainz
      • III. Department of Medicine
      Mainz, Rhineland-Palatinate, Germany
  • 2006–2013
    • National Heart, Lung, and Blood Institute
      • Division of Cardiovascular Sciences (DCVS)
      Maryland, United States
  • 1996–2013
    • Whitaker Wellness Institute
      Newport Beach, California, United States
  • 2011
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States
  • 2010
    • University of Texas Health Science Center at Houston
      • Human Genetics Center
      Houston, TX, United States
  • 2002–2010
    • Boston University
      • • Whitaker Cardiovascular Institute
      • • Section of Pulmonary, Allergy, Sleep, and Critical Care Medicine
      • • Department of Biostatistics
      Boston, MA, United States
    • University of Massachusetts Lowell
      • Department of Clinical Laboratory and Nutritional Sciences
      Lowell, Massachusetts, United States
  • 2009
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 2006–2008
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2003–2008
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Tufts Medical Center
      • Division of Cardiology
      Boston, Massachusetts, United States
  • 2007
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2005
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
  • 2004
    • University of New South Wales
      • Centre for Vascular Research (CVR)
      Kensington, New South Wales, Australia