Intra-city Differences in Cardiac Expression of Inflammatory Genes and Inflammasomes in Young Urbanites: A Pilot Study

Southwest Mexico City (SWMC) air pollution is characterized by high concentrations of ozone and particulate matter < 10 μm (PM10) containing lipopolysaccharides while in the North PM2.5 is high. These intra-city differences are likely accounting for higher CD14 and IL-1β in SWMC v NMC mice myocardial expression. This pilot study was designed to investigate whether similar intra-city differences exist in the levels of myocardial inflammatory genes in young people. Inflammatory mediator genes and inflammasome arrays were measured in right and left autopsy ventricles of 6 southwest/15 north (18.5 ± 2.6 years) MC residents after fatal sudden accidental deaths. There was a significant S v N right ventricle up-regulation of IL-1β (p=0.008), TNF-α (p=0.001), IL-10 (p=0.001), and CD14 (p=0.002), and a left ventricle difference in TNF-α (p=0.007), and IL-10 (p=0.02). SW right ventricles had significant up-regulation of NLRC1, NLRP3 and of 29/84 inflammasome genes, including NOD factors and caspases. There was significant degranulation of mast cells both in myocardium and epicardial nerve fibers. Differential expression of key inflammatory myocardial genes and inflammasomes are influenced by the location of residence. Myocardial inflammation and inflammasome activation in young hearts is a plausible pathway of heart injury in urbanites and adverse effects on the cardiovascular system are expected.

[1]  D. Brooks,et al.  Urban air pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection. , 2012, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[2]  Massimo Franchini,et al.  Thrombogenicity and cardiovascular effects of ambient air pollution. , 2011, Blood.

[3]  T. Nawrot,et al.  Public health importance of triggers of myocardial infarction: a comparative risk assessment , 2011, The Lancet.

[4]  Egil Lien,et al.  NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals , 2010, Nature.

[5]  Vicki Stone,et al.  Intracellular imaging of nanoparticles: Is it an elemental mistake to believe what you see? , 2010, Particle and Fibre Toxicology.

[6]  A. Peters,et al.  Particulate Matter Air Pollution and Cardiovascular Disease: An Update to the Scientific Statement From the American Heart Association , 2010, Circulation.

[7]  A. Knox,et al.  Endothelin-1 (ET-1) Increases the Expression of Remodeling Genes in Vascular Smooth Muscle through Linked Calcium and cAMP Pathways , 2010, The Journal of Biological Chemistry.

[8]  Philip B. Russell,et al.  An overview of the MILAGRO 2006 Campaign: Mexico City emissions and their transport and transformation , 2010 .

[9]  C. Reilly,et al.  Constriction of rat extra-splenic veins to lipopolysaccharide involves endothelin-1 , 2010, Naunyn-Schmiedeberg's Archives of Pharmacology.

[10]  F. Martinon Signaling by ROS drives inflammasome activation , 2010, European journal of immunology.

[11]  A. Cianciulli,et al.  Toll-like receptor 4 mediates LPS-induced release of nitric oxide and tumor necrosis factor-alpha by embryonal cardiomyocytes: biological significance and clinical implications in human pathology. , 2010, Current pharmaceutical design.

[12]  J. S. Janicki,et al.  Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart , 2010, Hypertension.

[13]  D. Golenbock,et al.  Inflammasomes: too big to miss. , 2009, The Journal of clinical investigation.

[14]  C. Bryant,et al.  Molecular mechanisms involved in inflammasome activation. , 2009, Trends in cell biology.

[15]  K. Kane,et al.  Mast cell degranulation – a mechanism for the anti‐arrhythmic effect of endothelin‐1? , 2009, British journal of pharmacology.

[16]  E. Golomb,et al.  Occult Cardiotoxicity—Toxic Effects on Cardiac Ischemic Tolerance , 2009, Toxicologic pathology.

[17]  N. Frangogiannis,et al.  The role of IL-1 in the pathogenesis of heart disease , 2009, Archivum Immunologiae et Therapiae Experimentalis.

[18]  Y. Yin,et al.  Inflammasomes are Differentially Expressed in Cardiovascular and other Tissues , 2009, International journal of immunopathology and pharmacology.

[19]  F. Martinon,et al.  The inflammasomes: guardians of the body. , 2009, Annual review of immunology.

[20]  G. Heusch,et al.  Tumor Necrosis Factor-&agr; and Its Receptors 1 and 2: Yin and Yang in Myocardial Infarction? , 2009, Circulation.

[21]  G. Wang,et al.  Divergent Tumor Necrosis Factor Receptor-Related Remodeling Responses in Heart Failure: Role of Nuclear Factor-&kgr;B and Inflammatory Activation , 2009, Circulation.

[22]  Mark R Holland,et al.  Intrinsic myoarchitectural differences between the left and right ventricles of fetal human hearts: an ultrasonic backscatter feasibility study. , 2009, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[23]  V. Dixit,et al.  Inflammasomes: guardians of cytosolic sanctity , 2009, Immunological reviews.

[24]  M. Lerner,et al.  Induction of cardiovascular pathology in a novel model of low-grade chronic inflammation. , 2009, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[25]  R. Schulz TNFalpha in myocardial ischemia/reperfusion: damage vs. protection. , 2008, Journal of molecular and cellular cardiology.

[26]  N. Bobrova,et al.  Pathomorphology of myocardial circulation: Comparative study in increased left or right ventricle afterload , 2008, Bulletin of Experimental Biology and Medicine.

[27]  K. Rock,et al.  Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization , 2008, Nature Immunology.

[28]  M. Boros,et al.  Modulation of cardiac contractility through endothelin-1 release and myocardial mast cell degranulation. , 2008, Acta physiologica Hungarica.

[29]  Richard A. Flavell,et al.  The Nalp3 inflammasome is essential for the development of silicosis , 2008, Proceedings of the National Academy of Sciences.

[30]  Mahipal Singh,et al.  Interleukin-1beta-mediated inhibition of the processes of angiogenesis in cardiac microvascular endothelial cells. , 2008, Life sciences.

[31]  A. Cianciulli,et al.  CD14 major role during lipopolysaccharide-induced inflammation in chick embryo cardiomyocytes. , 2008, FEMS immunology and medical microbiology.

[32]  J. Tschopp,et al.  Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica , 2008, Science.

[33]  C. Henríquez-Roldán,et al.  Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults , 2008, Toxicologic pathology.

[34]  A. Zaas,et al.  The effect of toll-like receptors and toll-like receptor genetics in human disease. , 2008, Annual review of medicine.

[35]  Guosheng Lin,et al.  TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI , 2008, Scandinavian cardiovascular journal : SCJ.

[36]  Mahipal Singh,et al.  Interleukin-1 β -mediated inhibition of the processes of angiogenesis in cardiac microvascular endothelial cells , 2008 .

[37]  M. Viana,et al.  PM speciation and sources in Mexico during the MILAGRO-2006 Campaign , 2007 .

[38]  M. Singer,et al.  Mechanisms of sepsis-induced cardiac dysfunction , 2007, Critical care medicine.

[39]  Qi Zhang,et al.  Detection of particle-phase polycyclic aromatic hydrocarbons in Mexico City using an aerosol mass spectrometer , 2007 .

[40]  M. Hazucha,et al.  Elevated Plasma Endothelin-1 and Pulmonary Arterial Pressure in Children Exposed to Air Pollution , 2007, Environmental health perspectives.

[41]  Jesús Serrano,et al.  Relations between PM10 composition and cell toxicity: a multivariate and graphical approach. , 2007, Chemosphere.

[42]  L. Cai,et al.  Elevation of serum endothelins and cardiotoxicity induced by particulate matter (PM2.5) in rats with acute myocardial infarction , 2007, Cardiovascular Toxicology.

[43]  Errol M. Thomson,et al.  Differential regulation of the lung endothelin system by urban particulate matter and ozone. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[44]  J. Maessen,et al.  Post-mortem histologic evaluation of microwave lesions after epicardial pulmonary vein isolation for atrial fibrillation. , 2005, The Annals of thoracic surgery.

[45]  R. Lekas,et al.  [Changes of cardiac electrophysiological parameters after destruction of epicardial nervous plexi innervating sinoatrial node]. , 2005, Kardiologiia.

[46]  D. Golenbock,et al.  Endotoxin recognition and signal transduction by the TLR4/MD2-complex. , 2004, Microbes and infection.

[47]  J. Wedemeyer,et al.  Mast cells promote homeostasis by limiting endothelin-1-induced toxicity , 2004, Nature.

[48]  J. S. Janicki,et al.  Endothelin-1 mediates cardiac mast cell degranulation, matrix metalloproteinase activation, and myocardial remodeling in rats. , 2004, American journal of physiology. Heart and circulatory physiology.

[49]  S. Gómez-Arroyo,et al.  The effects of seasonal weather on the genotoxicity, cytokinetic properties, cytotoxicity and organochemical content of extracts of airborne particulates in Mexico City. , 2004, Mutation research.

[50]  Jian-er Tang,et al.  Cardiomyocytes overexpressing TNF‐α attract migration of embryonic stem cells via activation of p38 and c‐Jun amino‐terminal kinase , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  D. Lees,et al.  A role for increased mRNA stability in the induction of endothelin-1 synthesis by lipopolysaccharide. , 2003, Biochemical pharmacology.

[52]  J. Miranda,et al.  Proinflammatory and cytotoxic effects of Mexico City air pollution particulate matter in vitro are dependent on particle size and composition. , 2003, Environmental health perspectives.

[53]  M. Thompson,et al.  Faecal contamination and enterotoxigenic Escherichia coli in street-vended chili sauces in Mexico and its public health relevance , 2002, Epidemiology and Infection.

[54]  R. Torres‐Jardón,et al.  Air Pollution Levels and Trends in the Mexico City Metropolitan Area , 2002 .

[55]  Tadashi Miyamoto,et al.  Neutralization of interleukin-1β in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling , 2001 .

[56]  R. Devlin,et al.  Canines as sentinel species for assessing chronic exposures to air pollutants: part 2. Cardiac pathology. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[57]  R. Lazzara,et al.  Cardiac denervation after transmyocardial laser. , 2001, The Annals of thoracic surgery.

[58]  A. Harken,et al.  Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function. , 1999, Critical care medicine.

[59]  C. Glembotski,et al.  LPS-induced TNF-alpha release from and apoptosis in rat cardiomyocytes: obligatory role for CD14 in mediating the LPS response. , 1998, Journal of molecular and cellular cardiology.

[60]  I. Adamson,et al.  Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1. , 1998, The American journal of pathology.

[61]  A. Matsumori,et al.  Cytokine gene expression after myocardial infarction in rat hearts: possible implication in left ventricular remodeling. , 1998, Circulation.

[62]  D. Meldrum Tumor necrosis factor in the heart. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[63]  D. Lynam,et al.  Personal exposure to elements in Mexico City air. , 1997, The Science of the total environment.

[64]  J. Polak,et al.  Distribution, morphology, and neurochemistry of endocardial and epicardial nerve terminal arborizations in the human heart. , 1995, Circulation.