RESUMO
This article focuses on screening the major secreted proteins by the ischemia-challenged cardiac stromal fibroblasts (CF), the assessment of their expression status and functional role in the post-ischemic left ventricle (LV) and in the ischemia-challenged CF culture and to phenotype CF at single cell resolution based on the positivity of the identified mediators. The expression level of CRSP2, HSP27, IL-8, Cofilin-1, and HSP90 in the LV tissues following coronary artery bypass graft (CABG) and myocardial infarction (MI) and CF cells followed the screening profile derived from the MS/MS findings. The histology data unveiled ECM disorganization, inflammation and fibrosis reflecting the ischemic pathology. CRSP2, HSP27, and HSP90 were significantly upregulated in the LV-CABG tissues with a concomitant reduction ion LV-MI whereas Cofilin-1, IL8, Nrf2, and Troponin I were downregulated in LV-CABG and increased in LV-MI. Similar trends were exhibited by ischemic CF. Single cell transcriptomics revealed multiple sub-phenotypes of CF based on their respective upregulation of CRSP2, HSP27, IL-8, Cofilin-1, HSP90, Troponin I and Nrf2 unveiling pathological and pro-healing phenotypes. Further investigations regarding the underlying signaling mechanisms and validation of sub-populations would offer novel translational avenues for the management of cardiac diseases.
Assuntos
Fibroblastos , Infarto do Miocárdio , Análise de Célula Única , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Fibroblastos/metabolismo , Humanos , Células Estromais/metabolismo , Interleucina-8/metabolismo , Interleucina-8/genética , Perfilação da Expressão Gênica , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP27/genética , Cofilina 1/metabolismo , Cofilina 1/genética , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Transcriptoma , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genéticaRESUMO
Atrial septal defects (ASD) are among the most common congenital heart diseases encountered in adulthood. Patent foramen ovale (PFO) is present in up to 25% of the population. ASD could present as isolated lesion or in association with more complex congenital heart disease form as tetralogy of Fallot, or Ebstein's anomaly of tricuspid valve. There is a wide range of clinical presentation ranging from asymptomatic subjects surviving to adulthood undiagnosed to subjects presenting with right heart failure and severe pulmonary vascular disease (Eisenmenger syndrome). This manuscript is an in depth review of the complex atrial septation, the variable clinical presentation of ASD and PFO, and its clinical and therapeutic implications.