Collagen isoform shift during the early phase of reverse left ventricular remodelling after relief of pressure overload.
OBJECTIVE
Aortic stenosis induces pressure overload and myocardial remodelling with concentric hypertrophy and alterations in extracellular matrix (ECM). Aortic valve replacement leads to reverse remodelling, a process of which knowledge is scarce. The aims of the present study were to examine alterations in myocardial gene expression and subsequently identify molecular alterations important for the early phase of reverse remodelling.


RESULTS
After 4 weeks of ascending aortic banding, mice were subjected to a debanding operation (DB) and followed for 3, 7, or 14 days. Cardiac function was assessed by echocardiography/tissue Doppler ultrasonography. Myocardial gene expression was examined using Affymetrix microarray and the topGO software and verified by real-time polymerase chain reaction. Quantitative measurements of collagen subtypes were performed. Aortic banding increased left ventricular mass by 60%, with normalization to sham level 14 days after DB. Extracellular matrix genes were the most regulated after DB. Three days after DB, collagen I was transiently increased, whereas collagens III and VIII increased later at 7 days.


CONCLUSIONS
The ECM genes were the most altered during reverse remodelling. There was a change in isoform constitution as collagen type I increased transiently at 3 days followed by a later increase in types III and VIII at 7 days after DB. This might be important for the biomechanical properties of the heart and recovery of cardiac function.
Bjørnstad
Johannes Lagethon
JL
Department of Cardiothoracic Surgery, Oslo University Hospital Ullevål, Oslo, Norway.
Sjaastad
Ivar
I
Nygård
Ståle
S
Hasic
Almira
A
Ahmed
Mohammad Shakil
MS
Attramadal
Håvard
H
Finsen
Alexandra Vanessa
AV
Christensen
Geir
G
Tønnessen
Theis
T
D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D002302:Cardiac Output / Q000502:physiology; D003094:Collagen / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009206:Myocardium / Q000737:chemistry; D020033:Protein Isoforms / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D018608:Ultrasonography, Doppler; D020257:Ventricular Remodeling / Q000502:physiology*
D015415:Biomarkers; D020033:Protein Isoforms; D012333:RNA, Messenger; D003094:Collagen