Cardiovascular Outcomes Following Xenobiotic Pulmonary Exposures
Holland, Nathan 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.
Holland, Nathan A.. (July 2017). Cardiovascular Outcomes Following Xenobiotic Pulmonary Exposures (Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/6364.)
Holland, Nathan A.. Cardiovascular Outcomes Following Xenobiotic Pulmonary Exposures. Doctoral Dissertation. East Carolina University, July 2017. The Scholarship. http://hdl.handle.net/10342/6364. February 23, 2020.
Holland, Nathan A., “Cardiovascular Outcomes Following Xenobiotic Pulmonary Exposures” (Doctoral Dissertation., East Carolina University, July 2017).
Holland, Nathan A.. Cardiovascular Outcomes Following Xenobiotic Pulmonary Exposures [Doctoral Dissertation]. Greenville, NC: East Carolina University; July 2017.
East Carolina University