Expression of laminin alpha2 chain during normal and pathological growth of myocardium in rat and human.
OBJECTIVE
Fibrosis is a classical feature of cardiac hypertrophy. To date changes within the basal lamina during normal and pathological cardiac growth have been poorly investigated. The goal of the present study was to determine if the expression of the muscle specific subunit of merosin (laminin alpha2 chain) together with that of fibronectin (FN) is modified in the diseased human heart. Laminin alpha2 chain expression was also investigated during physiological and pathological cardiac growth in the rat.


METHODS
In ten normal human hearts and ten hearts with idiopathic dilated cardiomyopathy (IDCM), the laminin-alpha2 and FN mRNA levels were quantified by slot-blot using total RNA and the protein distribution was analysed using an immunofluorescence approach. In Wistar rats, laminin alpha2 and FN mRNA expression was analyzed using RNase protection assay (RPA) and slot-blot assays.


RESULTS
The amount of laminin alpha2 mRNA did not vary in normal and pathological human hearts whereas it was significantly decreased in renovascular hypertensive rats (-20%) P<0.05 versus normal tissue). The amount of fibronectin mRNA increased in IDMC patients (x2, P<0.05 versus normal tissue), but was unchanged in hypertensive rats. A negative correlation was found between the cardiac laminin-alpha2 level and the age of the patients whatever the cardiac status. During postnatal development in the rat, a similar decrease in cardiac laminin-alpha2 level was observed between 3 and 30 weeks of age. Finally, the immunofluorescent approach failed to detect any alteration in laminin alpha2 distribution within the human myocardium.


CONCLUSIONS
These data indicate that an imbalance between myocyte hypertrophy and the level of laminin-alpha2 might contribute to alterations in sarcolemmal properties, which occur during the development of cardiac hypertrophy and its transition to cardiac failure.
Oliviéro
P
P
U127 INSERM, IFR-Circulation Paris VII, Hopital Lariboisière, 41 Bd Chapelle, Université D. Diderot, 75475, Paris, France.
Chassagne
C
C
Salichon
N
N
Corbier
A
A
Hamon
G
G
Marotte
F
F
Charlemagne
D
D
Rappaport
L
L
Samuel
J L
JL
D000704:Analysis of Variance; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005318:Fetal Heart / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006321:Heart / Q000254:growth & development; D006801:Humans; D006978:Hypertension, Renovascular; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D007797:Laminin; D020033:Protein Isoforms; D012333:RNA, Messenger; C102645:laminin alpha 2