Changes in extra cellular matrix remodelling and re-expression of fibronectin and tenascin-C splicing variants in human myocardial tissue of the right atrial auricle: implications for a targeted therapy of cardiovascular diseases using human SIP format antibodies.
Cardiovascular diseases are accompanied by changes in the extracellular matrix (ECM) including the re-expression of fibronectin and tenascin-C splicing variants. Using human recombinant small immunoprotein (SIP) format antibodies, a molecular targeting of these proteins is of therapeutic interest. Tissue samples of the right atrial auricle from patients with coronary artery disease and valvular heart disease were analysed by PCR based ECM gene expression profiling. Moreover, the re-expression of fibronectin and tenascin-C splicing variants was investigated by immunofluoerescence labelling. We demonstrated changes in ECM gene expression depending on histological damage or underlying cardiac disease. An increased expression of fibronectin and tenascin-C mRNA in association to histological damage and in valvular heart disease compared to coronary artery disease could be shown. There was a distinct re-expression of ED-A containing fibronectin and A1 domain containing tenascin-C detectable with human recombinant SIP format antibodies in diseased myocardium. ED-A containing fibronectin showed a clear vessel positivity. For A1 domain containing tenascin-C, there was a particular positivity in areas of interstitial and perivascular fibrosis. Right atrial myocardial tissue is a valuable model to investigate cardiac ECM remodelling. Human recombinant SIP format antibodies usable for an antibody-mediated targeted delivery of drugs might offer completely new therapeutic options in cardiac diseases.
Franz
Marcus
M
Department of Internal Medicine I, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany. Marcus.Franz@med.uni-jena.de
Brehm
Bernhard R
BR
Richter
Petra
P
Gruen
Katja
K
Neri
Dario
D
Kosmehl
Hartwig
H
Hekmat
Khosro
K
Renner
Andre
A
Gummert
Jan
J
Figulla
Hans R
HR
Berndt
Alexander
A
D017398:Alternative Splicing / Q000235:genetics*; D000906:Antibodies / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D006349:Heart Valve Diseases / Q000235:genetics / Q000473:pathology; D006801:Humans; D007162:Immunoproteins / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism
D000906:Antibodies; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D007162:Immunoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D019063:Tenascin