{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:09:49Z","timestamp":1791194989051,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The mechanistic links between exposure to airborne particulate matter (PM) pollution and the associated increases in cardiovascular morbidity and mortality, particularly in people with congestive heart failure (CHF), have not been identified. To advance understanding of this issue, genetically engineered mice (CREBA133) exhibiting severe dilated cardiomyopathic changes were exposed to ambient PM collected in Baltimore. CREBA133 mice, which display aberrant cardiac physiology and anatomy reminiscent of human CHF, displayed evidence of basal autonomic aberrancies (compared with wild-type mice) with PM exposure via aspiration, producing significantly reduced heart rate variability, respiratory dysynchrony, and increased ventricular arrhythmias. Carotid body afferent nerve responses to hypoxia and hyperoxia-induced respiratory depression were pronounced in PM-challenged CREBA133 mice, and denervation of the carotid bodies significantly reduced PM-mediated cardiac arrhythmias. Genome-wide expression analyses of CREBA133 left ventricular tissues demonstrated prominent Na+ and K+ channel pathway gene dysregulation. Subsequent PM challenge increased tyrosine phosphorylation and nitration of the voltage-gated type V cardiac muscle \u03b1-subunit of the Na+ channel encoded by SCN5A. Ranolazine, a Na+ channel modulator that reduces late cardiac Na+ channel currents, attenuated PM-mediated cardiac arrhythmias and shortened PM-elongated QT intervals in vivo. These observations provide mechanistic insights into the epidemiologic findings in susceptibility of human CHF populations to PM exposure. Our results suggest a multiorgan pathobiology inherent to the CHF phenotype that is exaggerated by PM exposure via heightened carotid body sensitivity and cardiac Na+ channel dysfunction.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0213oc","type":"journal-article","created":{"date-parts":[[2011,11,23]],"date-time":"2011-11-23T00:40:55Z","timestamp":1322008855000},"page":"524-531","source":"Crossref","is-referenced-by-count":47,"title":["Particulate Matter Induces Cardiac Arrhythmias via Dysregulation of Carotid Body Sensitivity and Cardiac Sodium Channels"],"prefix":"10.1093","volume":"46","author":[{"given":"Ting","family":"Wang","sequence":"first","affiliation":[{"name":"Sections of Pulmonary, Critical Care, Sleep & Allergy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel D.","family":"Lang","sequence":"additional","affiliation":[{"name":"Sections of Pulmonary, Critical Care, Sleep & Allergy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Moreno-Vinasco","sequence":"additional","affiliation":[{"name":"Sections of Pulmonary, Critical Care, Sleep & Allergy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha N.","family":"Goonewardena","sequence":"additional","affiliation":[{"name":"Sections of Pulmonary, Critical Care, Sleep & Allergy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2013Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Emergency Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Svensson","sequence":"additional","affiliation":[{"name":"Sections of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viswanathan","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Sections of Pulmonary, Critical Care, Sleep & Allergy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto M.","family":"Lang","sequence":"additional","affiliation":[{"name":"Sections of Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jered D.","family":"Linares","sequence":"additional","affiliation":[{"name":"Sections of Pulmonary, Critical Care, Sleep & Allergy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick N.","family":"Breysse","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison S.","family":"Geyh","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Samet","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Southern California, Los Angeles, California; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves A.","family":"Lussier","sequence":"additional","affiliation":[{"name":"Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Dudley","sequence":"additional","affiliation":[{"name":"Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanduri R.","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Emergency Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe G. 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