RESUMEN
Vascular calcification predicts an increased risk for cardiovascular events in atherosclerosis, diabetes, and end-stage kidney diseases. Matrix Gla protein (MGP), an inhibitor of calcification, limits calcium phosphate deposition in the vessel wall. There are many factors contributing to the progression of atherosclerosis, including hypertension, hyperlipidemia, the renin-angiotensin system, and inflammation. Angiotensin II (ANG II) plays a crucial role in the atherogenic process through not only its pressor responses but also its growth-promoting and inflammatory effects. In this study, we investigated the role of MGP in ANG II-induced exacerbation of vascular calcification in human vascular smooth muscle cells (VSMCs). The expression of MGP, calcification, and apoptosis in human VSMCs were examined by Western blot analysis, real-time PCR, in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and enzyme-linked immunosorbent assay, respectively. Increase in VSMC calcification in human atherosclerotic plaques upregulates MGP expression and apoptosis in a negative feedback manner. ANG II inhibited MGP expression in VSMCs via and in vitro in a dose- and time-dependent manner through ANG II type 1 receptor and NF-κB signaling pathway. Meanwhile, MGP inhibited the calcification, caspase-3 activity, activation of runt-related transcription factor 2, and release of inflammatory cytokines by VSMCs induced by calcification medium (2.5 mM P(i)) and ANG II in vitro. These observations provide evidence that ANG II exacerbates vascular calcification through activation of the transcription factors, runt-related transcription factor 2 and NF-κB, and regulation of MGP, inflammatory cytokines expression in human VSMCs.
Asunto(s)
Angiotensina II/metabolismo , Proteínas de Unión al Calcio/metabolismo , Enfermedades de las Arterias Carótidas/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/metabolismo , Anciano , Apoptosis , Western Blotting , Fosfatos de Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Arterias Carótidas/metabolismo , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/genética , Enfermedades de las Arterias Carótidas/inmunología , Enfermedades de las Arterias Carótidas/patología , Caspasa 3/metabolismo , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Citocinas/metabolismo , Activación Enzimática , Ensayo de Inmunoadsorción Enzimática , Proteínas de la Matriz Extracelular/genética , Retroalimentación Fisiológica , Regulación de la Expresión Génica , Humanos , Etiquetado Corte-Fin in Situ , Mediadores de Inflamación/metabolismo , Persona de Mediana Edad , Músculo Liso Vascular/inmunología , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/inmunología , Miocitos del Músculo Liso/patología , FN-kappa B/metabolismo , Placa Aterosclerótica , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor de Angiotensina Tipo 1/metabolismo , Transducción de Señal , Factores de Tiempo , Transfección , Calcificación Vascular/genética , Calcificación Vascular/inmunología , Calcificación Vascular/patología , Proteína Gla de la MatrizRESUMEN
BACKGROUND: The role of peer teachers in interprofessional education has not been extensively studied. This study is designed to determine if peer-teacher-led problem-based seminars can influence medical and pharmacy students' perceptions of interprofessional education. METHODS: Undergraduate medical and pharmacy students participated in one-hour problem-based learning seminars held over the course of 16 weeks. A case-control study design was used to compare perceptions of interprofessional education between students who participated in seminars and students who did not participate in seminars. The validated Interdisciplinary Education Perception Scale (IEPS) was used to assess perceptions of interprofessional education and was distributed to medical and pharmacy students at the conclusion of 16 weeks of seminars. A two-tailed t-test was used to determine significance between groups. A survey was also distributed to all students regarding perceived barriers to involvement in interprofessional education training. RESULTS: In total, 97 students responded to IEPS (62 medical, 35 pharmacy). Data showed significantly higher perception of professional cooperation among medical students (p=0.006) and pharmacy students (p=0.02) who attended interprofessional seminars compared to those who did not attend. One hundred and nine students responded to the survey regarding perceived barriers to interprofessional education, with the two most common barriers being: 'I am not aware of interprofessional education opportunities' (61.5%) and 'I do not have time to participate' (52.3%). CONCLUSION: Based on this data we believe peer-teacher-led problem-based interprofessional seminars can be used to increase medical and pharmacy students' perceived need for professional cooperation. Currently, major barriers to interprofessional education involvement are awareness and time commitment. Undergraduate health professions education can incorporate student-led seminars to improve interprofessional education.