OBJECTIVES: Peroxisome proliferator-activated receptor-a is significantly down-regulated in circulating leukocytes from @entity1 with @entity295 . Peroxisome proliferator-activated receptor-a null (Ppara) @entity19 have greater mortality than wild-type @entity19 when subjected to @entity295 by cecal ligation and puncture. We sought to characterize the role of peroxisome proliferator-activated receptor-a in @entity295 and to identify the mechanism whereby peroxisome proliferator-activated receptor-a confers a survival advantage. DESIGN: Prospective randomized preclinical study. SETTING: Laboratory investigation. SUBJECTS: Male C57Bl/6J and Ppara @entity19 (B6.129S4-Ppara/J), aged 12-16 weeks. INTERVENTIONS: Bone marrow chimeric @entity19 were generated and subjected to cecal ligation and puncture. Survival was measured for 7 days. Separate groups of nontransplanted @entity19 underwent cecal ligation and puncture and were euthanized 24 hours later for plasma and tissue analyses. MEASUREMENTS AND MAIN RESULTS: Ppara @entity19 had dramatically reduced survival compared with wild-type @entity19 irrespective of the peroxisome proliferator-activated receptor-a status of the bone marrow they received (3% vs 63%; p < 0.0001). No difference in survival was observed between Ppara @entity19 that received wild-type versus Ppara marrow or in wild-type @entity19 receiving wild-type versus Ppara marrow. In septic, nontransplanted @entity19 at 24 hours, Ppara @entity19 had elevated cardiac troponin levels compared with wild-type @entity19 . Cardiac histologic injury scores were greater in Ppara versus wild-type @entity19 . Expression of transcription factors and enzymes related to @entity844 oxidation in the heart were profoundly down-regulated in both wild-type and Ppara @entity19 , but more so in the Ppara @entity19 . CONCLUSIONS: Peroxisome proliferator-activated receptor-a expression in nonhematopoietic tissues plays a critical role in determining clinical outcome in experimental polymicrobial @entity295 and is more important to survival in @entity295 than hematopoietic peroxisome proliferator-activated receptor-a expression. @entity299 due to inadequate energy production from @entity844 substrate is a probable mechanism of decreased survival in Ppara @entity19 . These results suggest that altered peroxisome proliferator-activated receptor-a-mediated cellular metabolism may play an important role in @entity295 -related end-organ @entity66 , especially in the heart.

Nonhematopoietic Peroxisome Proliferator-Activated Receptor-a Protects Against XXXX and Enhances Survival in Experimental Polymicrobial Sepsis.

@entity1 :: ('9606', 'Species') :: ['children'] @entity844 :: ('CHEBI:35366', 'Chemical') :: ['fatty acid'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity66 :: ('MESH:D004194', 'Disease') :: ['injury and dysfunction'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity299 :: ('MESH:D006331', 'Disease') :: ['Cardiac injury']
@entity299 :: (MESH:D006331,Disease) :: ['Cardiac Injury']
