Genomic profiling of left and right ventricular hypertrophy in congenital heart disease.
BACKGROUND
The right ventricle (RV) has a lower ability than the left ventricle (LV) to adapt to systemic load. The molecular basis of these differences is not known. We compared hypertrophy-signaling pathways between the RV and the LV in patients with congenital heart disease (CHD).


METHODS
Gene expression was measured using DNA microarrays in myocardium from children with CHD with LV or RV obstructive lesions undergoing surgery. The expression of 175 hypertrophy-signaling genes was compared between the LV (n=7) and the RV (n=11). Hierarchic clustering was performed.


RESULTS
Seventeen genes (10%) were differentially expressed between the LV and the RV. Expression of genes for angiotensin, adrenergic, G-proteins, cytoskeletal, and contractile components was lower (P < .05) and expression of maladaptive factors (fibroblast growth factors, transforming growth factor-beta, caspases, ubiquitin) was higher in the RV compared with the LV (P < .05). Five of 7 LV samples clustered together. Only 4 of 11 RV samples clustered with the LV. Genes critical to adaptive remodeling correlated with the degree of LV hypertrophy but not RV hypertrophy.


CONCLUSIONS
The transcription of pathways of adaptive remodeling was lower in the RV compared with the LV. This may explain the lower ability of the RV to adapt to hemodynamic load in CHD.
Kaufman
Beth D
BD
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Desai
Manisha
M
Reddy
Sushma
S
Osorio
Juan Carlos
JC
Chen
Jonathan M
JM
Mosca
Ralph S
RS
Ferrante
Anthony W
AW
Mital
Seema
S
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015150:Echocardiography, Doppler; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics / Q000379:methods; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics*; D017380:Hypertrophy, Right Ventricular / Q000000981:diagnostic imaging / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult