2-Chlorofatty Acid: A Novel Lipid Mediator of Endothelial Dysfunction during Sepsis
Başlık:
2-Chlorofatty Acid: A Novel Lipid Mediator of Endothelial Dysfunction during Sepsis
Yazar:
Hartman, Celine L., author.
ISBN:
9780438127807
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (160 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: David A. Ford Committee members: Angel Baldan; Jane McHowat.
Özet:
Sepsis is a complex, life-threatening complication to an infection. Neutrophils play a key role in anti-microbial defense during sepsis, but these abundant immune cells can also damage host tissue. For instance, neutrophil-derived 2-chlorofatty acids are produced under inflammatory conditions and have deleterious effects on neutrophils and surrounding endothelial cells. Neutrophil-produced hypochlorous acid targets the vinyl ether bond of plasmalogen phospholipids to produce the chlorinated lipidome. Chlorinated lipids, and other bioactive lipids, are currently being investigated for their roles in sepsis. In this dissertation, data is presented to support a novel hypothesis that 2-chlorofatty acids, the stable chlorinated lipid metabolites, elicit endothelial dysfunction and are important during the progression of sepsis. Chapter 3 demonstrates the potential utility of plasma 2-chlorofatty acids as a prognostic indicator of lung injury and 30-day mortality in human sepsis subjects. Chapter 4 provides a mechanistic role for 2-chlorofatty acids during sepsis through their localization in Weibel-Palade bodies and induction of endothelial dysfunction, a critical event for sepsis progression. To investigate the mechanism by which 2-chlorofatty acids elicit endothelial dysfunction, Chapter 5 examined the ability of 2-chlorofatty acids to bind to cellular proteins and revealed two novel mechanisms through modification of cysteine residues. Finally, platelet-activating factor is another bioactive lipid, which may have a role in sepsis progression. A novel method to accurately quantify low levels of platelet-activating factor was demonstrated in Chapter 6. Taken together, this dissertation provides multiple key insights into the roles of bioactive lipids in sepsis.
Notlar:
School code: 0193
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(693504.1) | 693504-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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