RESUMO
Pulmonary arterial hypertension (PAH) is a progressive, devastating disease, and its main histological manifestation is an occlusive pulmonary arteriopathy. One important functional component of PAH is aberrant endothelial cell (EC) function including apoptosis-resistance, unchecked proliferation, and impaired migration. The mechanisms leading to and maintaining physiologic and aberrant EC function are not fully understood. Here, we tested the hypothesis that in PAH, ECs have increased expression of the transmembrane protein integrin-ß5, which contributes to migration and survival under physiologic and pathological conditions, but also to endothelial-to-mesenchymal transition (EnMT). We found that elevated integrin-ß5 expression in pulmonary artery lesions and lung tissue from PAH patients and rats with PH induced by chronic hypoxia and injection of CD117+ rat lung EC clones. These EC clones exhibited elevated expression of integrin-ß5 and its heterodimerization partner integrin-αν and showed accelerated barrier formation. Inhibition of integrin-ανß5 in vitro partially blocked transforming growth factor (TGF)-ß1-induced EnMT gene expression in rat lung control ECs and less in rat lung EC clones and human lung microvascular ECs. Inhibition of integrin-ανß5 promoted endothelial dysfunction as shown by reduced migration in a scratch assay and increased apoptosis in synergism with TGF-ß1. In vivo, blocking of integrin-ανß5 exaggerated PH induced by chronic hypoxia and CD117+ EC clones in rats. In summary, we found a role for integrin-ανß5 in lung endothelial survival and migration, but also a partial contribution to TGF-ß1-induced EnMT gene expression. Our results suggest that integrin-ανß5 is required for physiologic function of ECs and lung vascular homeostasis.
RESUMO
BACKGROUND: The importance of preoperative urinary tract infection (UTI) in total hip and knee arthroplasty (THA and TKA) is controversial. The purpose of this study was to investigate the timing of preoperative UTI diagnosis and association with prosthetic joint infection (PJI) and determine if antibiotics impact this risk. METHODS: A national database was used to analyze patients undergoing THA and TKA diagnosed with a preoperative UTI. Timing of diagnosis was categorized by 1-week intervals prior to surgery. Matched cohorts without UTI were collected, and PJI rates within 2 years of surgery were compared. Patients who received antibiotic prescriptions were identified and compared to no prescription. RESULTS: Preoperative UTI within 1 week of TKA was associated with higher rates of PJI (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.26-1.43, P < .001). Preoperative UTI within 1 week of THA (OR 1.56, 95% CI 1.44-1.68, P < .001) and between 1-2 weeks prior to THA (OR 1.12, 95% CI 1.02-1.22, P = .022) was associated with significantly higher rates of PJI. UTI diagnosis at any other time interval did not reach statistical significance. Antibiotic prescription was not associated with lower rates of PJI. CONCLUSION: Patients with preoperative UTI within 1 week of TKA or within 2 weeks of THA have an increased risk of postoperative PJI. Antibiotics do not appear to mitigate risk. LEVEL OF EVIDENCE: Level III; Retrospective, database comparison.
