RESUMEN
AIMS: Neointima formation after vascular injury is strongly associated with inflammation. Rapamycin inhibits human neointima formation and reduces expression of the proinflammatory cytokine endothelial-monocyte activating peptide II (EMAP-II) in vitro. Here we investigated the interplay between EMAP-II and rapamycin after vascular injury in vivo. METHODS AND RESULTS: In a mouse model of vascular injury, mice were either not treated, given everolimus, a rapamycin derivate, or subjected to simultaneous challenge with everolimus and EMAP-II. EMAP-II expression was measured in coronary artery smooth muscle cells (CASMC) and monocytic cells in vitro and in patients after percutaneous coronary intervention (PCI). After vascular injury, rapamycin reduced neointima formation and adventitial thickening. Immunohistochemistry revealed reduced EMAP-II protein expression and suppressed recruitment of inflammatory cells. Simultaneous challenge with EMAP-II counteracted these effects of rapamycin. Expression of EMAP-II and its inhibition by rapamycin was confirmed in CASMC and monocytic cells. In patients, EMAP-II upregulation was confined to PCI of distal coronary artery segments and profoundly suppressed by oral rapamycin treatment. CONCLUSION: These data suggest important yet unrecognized roles of EMAP-II and adventitial inflammation in neointima formation: Through inhibition of EMAP-II, rapamycin reduces the recruitment of inflammatory cells to the adventitia and supports an early and bland healing.
Asunto(s)
Citocinas/fisiología , Proteínas de Neoplasias/fisiología , Proteínas de Unión al ARN/fisiología , Sirolimus/farmacología , Túnica Íntima/patología , Angioplastia Coronaria con Balón , Animales , Apoptosis , Células Cultivadas , Reestenosis Coronaria/prevención & control , Vasos Coronarios/patología , Regulación hacia Abajo , Inflamación/etiología , Macrófagos/fisiología , Ratones , Sirolimus/antagonistas & inhibidoresRESUMEN
In our society, state governments have the major role in regulating physician behavior and actions related to end-of-life decision making. However, in the current confusing and conflicted legal environment, how well are state governments doing with this serious responsibility? The authors of this article report the results of the first statewide survey of Louisiana physicians regarding their knowledge of and compliance with specific parts of one state government's attempt to regulate end-of-life decision making: the Louisiana Natural Death Act (LNDA). Physician respondents were asked to indicate their level of familiarity with the LNDA and several questions examined physician compliance with specific sections contained in the statute. Among many things, the survey revealed most physicians (74%) were not familiar with even the basic provisions of the LNDA, and had not received either medical school or subsequent post graduate training in this area. Based on the results of this survey, the authors offer several policy recommendations that could enhance physician knowledge and subsequent compliance with the LNDA.