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Detrimental Effects Of Pcsk9 Loss-Of-Function In The Pediatric Host Response To Sepsis Are Mediated Through Independent Influence On Angiopoietin-1., Mihir R. Atreya, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam J. Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N. Alder, Patrick Lahni, Scarlett Ripberger, Adesuwa Ekunwe, Kyle R. Campbell, Keith R. Walley, Stephen W. Standage
Detrimental Effects Of Pcsk9 Loss-Of-Function In The Pediatric Host Response To Sepsis Are Mediated Through Independent Influence On Angiopoietin-1., Mihir R. Atreya, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam J. Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N. Alder, Patrick Lahni, Scarlett Ripberger, Adesuwa Ekunwe, Kyle R. Campbell, Keith R. Walley, Stephen W. Standage
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults. In contrast, we have previously demonstrated higher mortality in the juvenile host. Given the potential pleiotropic effects of PCSK9 on the endothelium, beyond canonical effects on serum lipoproteins, both of which may influence sepsis outcomes, we sought to test the influence of PCSK9 LOF genotype on endothelial dysfunction.
METHODS: Secondary analyses of a prospective observational cohort of pediatric septic shock. Genetic variants …
Necrotizing Enterocolitis In Premature Infants-A Defect In The Brakes? Evidence From Clinical And Animal Studies., Venkatesh Sampath, Maribel Martinez, Michael Caplan, Mark A. Underwood, Alain Cuna
Necrotizing Enterocolitis In Premature Infants-A Defect In The Brakes? Evidence From Clinical And Animal Studies., Venkatesh Sampath, Maribel Martinez, Michael Caplan, Mark A. Underwood, Alain Cuna
Manuscripts, Articles, Book Chapters and Other Papers
A key aspect of postnatal intestinal adaptation is the establishment of symbiotic relationships with co-evolved gut microbiota. Necrotizing enterocolitis (NEC) is the most severe disease arising from failure in postnatal gut adaptation in premature infants. Although pathological activation of intestinal Toll-like receptors (TLRs) is believed to underpin NEC pathogenesis, the mechanisms are incompletely understood. We postulate that unregulated aberrant TLR activation in NEC arises from a failure in intestinal-specific mechanisms that tamponade TLR signaling (the brakes). In this review, we discussed the human and animal studies that elucidate the developmental mechanisms inhibiting TLR signaling in the postnatal intestine (establishing the …