Gene expression profile analysis of aortic vascular smooth muscle cells reveals upregulation of cadherin genes in myocardial infarction patients.
Physiol Genomics
; 50(8): 648-657, 2018 08 01.
Article
en En
| MEDLINE
| ID: mdl-29775430
ABSTRACT
Myocardial infarction (MI) induced by acute coronary arterial occlusion is usually secondary to atherosclerotic plaque rupture. Dysregulated response of vascular smooth muscle cells (VSMCs) in atherosclerotic plaques may promote plaque rupture. Cadherins (CDHs) form adherens junctions and are known stabilizers of atherosclerotic plaques. To date, the expression patterns of cadherin have not been well investigated in MI aortic VSMCs. We aimed to investigate the expression of cadherin genes in the aortic wall of patients with and without MI. Laser capture microdissected VSMCs were obtained from aortic tissue samples of patients undergoing coronary artery bypass graft surgery. Integrative bioinformatic analysis of the microarray profiles of the VSMCs revealed that MI is discriminated at the whole transcriptome level by hundreds of differentially expressed genes, including genes involved in cell adhesion, of which the cadherin superfamily genes were among the top structural category. Eleven significantly deregulated candidates of the cadherin superfamily were chosen and formed a new classifier that collectively discriminated MI vs. non-MI with ~95% accuracy. Significance validation was performed with an independent cohort by quantitative RT-quantitative PCR, confirming overexpression of CDH2, CDH12, PCDH17, and PCDH18 in MI VSMCs. The dysregulation of these cadherin superfamily genes might be related to an MI-induced remote effect on aortic wall VSMCs and to imbalances in signaling pathways and myocardial repair mechanisms. Although pathophysiological significance of our findings requires functional studies, mRNA upregulation of the identified cadherin superfamily members in VSMCs might be associated with the progression of atherosclerosis and angiogenesis activation in MI.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cadherinas
/
Regulación hacia Arriba
/
Perfilación de la Expresión Génica
/
Miocitos del Músculo Liso
/
Infarto del Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Physiol Genomics
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania