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035 a| (Sirsi) o1001281831;

035 a| (OCoLC)1001281831;

049 a| EREE;

100 1 a| Holland, Nathan A.,e| author.?| UNAUTHORIZED;

245 10 a| Cardiovascular outcomes following xenobiotic pulmonary exposures /c| by Nathan A. Holland.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2017.;

300 a| 245 pages :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 87.08 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph. D.c| East Carolina Universityd| 2017;

500 a| Presented to the faculty of the Department of Physiology;

500 a| Advisor: Robert Lust;

500 a| Title from PDF t.p. (viewed December 14, 2017).;

520 3 a| Cardiovascular disease remains the leading cause of mortality in the developed world. Over the past decades, investigations have demonstrated that pulmonary exposure to xenobiotic particulate matter promotes and exacerbates cardiovascular disease including myocardial infarction. The impact of particulate matter on cardiovascular health has served as a backdrop concern raising questions regarding the potential exposure risks to the plethora of naturally occurring, industrial or combustion by-product, and engineered PM. Given historical trends towards increased human exposure to PM, as well as the mounting prevalence of CVD understanding the synergistic relationship between PM exposures and CVD is crucial. As a result, investigations of PM-induced mechanisms of toxicity have grown in kind. Despite this effort the putative mechanisms that underlie CVD and exposure to PM remain elusive. We set out to explore the potential mechanisms that result in cross-talk between the pulmonary and cardiovascular systems whereby exposure to various forms of PM is capable of inducing expansion of cardiac ischemia-reperfusion (I/R) injury. These mechanisms include mitochondrial dysfunction, alterations in vascular reactivity, and increased sensitivity to cytokine mediated inflammation. Following exposure to silver nanoparticles (AgNP) or multiwalled carbon nanotubes (MWCNT) we observed expansion of cardiac ischemia reperfusion injury, increased mitochondrial sensitivity to Ca++ leading to mitochondrial transition, elevations in circulating cytokines, including IL-6, independent of gross pulmonary injury, as well as coronary vascular dysfunction. Furthermore, we uncovered a relationship between PM exposures and up-regulation of IL-6 trans-signaling. The link between PM, cardiac I/R injury and IL-6 trans-signaling led to investigation of the potential role for IL-6 and its trans-signaling mechanism in the setting of acute myocardial infarction. We conclude that exposure to PM primes organ systems to over-respond to a secondary insult i.e. cardiac I/R injury, however the mechanisms that drive this response remain elusive.;

504 a| Includes bibliographical references.;

650 2 a| Cardiovascular Diseases.=| ^A918029;

650 2 a| Xenobiotics.=| ^A1018040;

650 2 a| Lung.=| ^A918175;

650 2 a| Particulate Matter.=| ^A947401;

653 a| Ischemia;

653 a| Reperfusion;

653 a| Myocardial Infarction;

653 a| Vascular;

653 a| IL-6;

700 1 a| Lust, Robert M.,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Physiology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/6364;

949 o| wjh;

994 a| C0b| ERE;

096 a| WG 120;

596 a| 1 4;

998 a| 4733403;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4733403-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 8/16/2017x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4733403-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 8/16/2017x| ETDz| HERESOURCE;

Cardiovascular outcomes following xenobiotic pulmonary exposures / by Nathan A. Holland.

Author/creator	Holland, Nathan A. author.
Other author	Lust, Robert M., degree supervisor.
Other author	East Carolina University. Department of Physiology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2017.
Description	245 pages : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Cardiovascular Diseases. Xenobiotics. Lung. Particulate Matter.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Cardiovascular disease remains the leading cause of mortality in the developed world. Over the past decades, investigations have demonstrated that pulmonary exposure to xenobiotic particulate matter promotes and exacerbates cardiovascular disease including myocardial infarction. The impact of particulate matter on cardiovascular health has served as a backdrop concern raising questions regarding the potential exposure risks to the plethora of naturally occurring, industrial or combustion by-product, and engineered PM. Given historical trends towards increased human exposure to PM, as well as the mounting prevalence of CVD understanding the synergistic relationship between PM exposures and CVD is crucial. As a result, investigations of PM-induced mechanisms of toxicity have grown in kind. Despite this effort the putative mechanisms that underlie CVD and exposure to PM remain elusive. We set out to explore the potential mechanisms that result in cross-talk between the pulmonary and cardiovascular systems whereby exposure to various forms of PM is capable of inducing expansion of cardiac ischemia-reperfusion (I/R) injury. These mechanisms include mitochondrial dysfunction, alterations in vascular reactivity, and increased sensitivity to cytokine mediated inflammation. Following exposure to silver nanoparticles (AgNP) or multiwalled carbon nanotubes (MWCNT) we observed expansion of cardiac ischemia reperfusion injury, increased mitochondrial sensitivity to Ca++ leading to mitochondrial transition, elevations in circulating cytokines, including IL-6, independent of gross pulmonary injury, as well as coronary vascular dysfunction. Furthermore, we uncovered a relationship between PM exposures and up-regulation of IL-6 trans-signaling. The link between PM, cardiac I/R injury and IL-6 trans-signaling led to investigation of the potential role for IL-6 and its trans-signaling mechanism in the setting of acute myocardial infarction. We conclude that exposure to PM primes organ systems to over-respond to a secondary insult i.e. cardiac I/R injury, however the mechanisms that drive this response remain elusive.
General note	Presented to the faculty of the Department of Physiology
General note	Advisor: Robert Lust
General note	Title from PDF t.p. (viewed December 14, 2017).
Dissertation note	Ph. D. East Carolina University 2017
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Cardiovascular outcomes following xenobiotic pulmonary exposures / by Nathan A. Holland.

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