title: New Cell Adhesion Molecules in Human Ischemic Cardiomyopathy. PCDHGA3 Implications in Decreased Stroke Volume and Ventricular Dysfunction.
abstract: BACKGROUND
  Intercalated disks are unique structures in cardiac tissue, in which adherens junctions, desmosomes, and GAP junctions co-localize, thereby facilitating cardiac muscle contraction and function. Protocadherins are involved in these junctions; however, their role in heart physiology is poorly understood. We aimed to analyze the transcriptomic profile of adhesion molecules in patients with ischemic cardiomyopathy (ICM) and relate the changes uncovered with the hemodynamic alterations and functional depression observed in these patients.
  
  
  RESULTS
  Twenty-three left ventricular tissue samples from patients diagnosed with ICM (n = 13) undergoing heart transplantation and control donors (CNT, n = 10) were analyzed using RNA sequencing. Forty-two cell adhesion genes involved in cellular junctions were differentially expressed in ICM myocardium. Notably, the levels of protocadherin PCDHGA3 were related with the stroke volume (r = -0.826, P = 0.003), ejection fraction (r = -0.793, P = 0.004) and left ventricular end systolic and diastolic diameters (r = 0.867, P = 0.001; r = 0.781, P = 0.005, respectively).
  
  
  CONCLUSIONS
  Our results support the importance of intercalated disks molecular alterations, closely involved in the contractile function, highlighting its crucial significance and showing gene expression changes not previously described. Specifically, altered PCDHGA3 gene expression was strongly associated with reduced stroke volume and ventricular dysfunction in ICM, suggesting a relevant role in hemodynamic perturbations and cardiac performance for this unexplored protocadherin.
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gil-Cayuela
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Manzanares
authors.affiliation: Cardiovascular Surgery Service, University and Polytechnic La Fe Hospital, Valencia, Spain.
authors.forename: José Anastasio
authors.initials: JA
authors.lastname: Montero
authors.affiliation: Cardiology Service of Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cinca
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.affiliation: Cardiocirculatory Unit, The Health Research Institute La Fe, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
mesh_terms: D015153:Blotting, Western; D000070585:Cadherin Related Proteins; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D013318:Stroke Volume / Q000235:genetics*; D059467:Transcriptome; D018754:Ventricular Dysfunction / Q000235:genetics*
chemical_list: D000070585:Cadherin Related Proteins; D015815:Cell Adhesion Molecules; C000608359:PCDH-GAMMA-A3, human