The pathway of tissue
aldosterone production may exist in the heart, and may be an important contributory factor to myocardial
fibrosis and cardiac remodelling in the failing heart.
CYP11B2 (
aldosterone synthase) catalyses the final step of
aldosterone production. The aim of the present study was to determine whether
CYP11B2 and
CYP11B1 (11beta-hydroxylase) are expressed in myocardial tissues, and whether these
enzymes contribute to
collagen accumulation and myocardial dysfunction in the failing human heart. Endomyocardial tissues were obtained from 23 patients with chronic
heart failure (CHF) and 10 controls.
CYP11B2 and
CYP11B1 mRNA levels were measured by real-time quantitative
reverse transcriptase-PCR. The myocardial
collagen volume fraction (CVF) was determined by digital planimetry.
CYP11B2 mRNA expression was greater in the CHF group than in the controls (P<0.05), while
CYP11B1 mRNA was barely expressed in either group. There was a positive correlation between
CYP11B2 mRNA levels and CVF (r=0.64, P=0.001).
CYP11B2 mRNA was particularly highly expressed in subgroups of CHF patients with a large left ventricular end-systolic diameter (>55 mm) or a low left ventricular ejection fraction (<30%).
CYP11B2 mRNA expression and CVF were lower in a CHF subgroup treated with a combination of
spironolactone and
angiotensin-converting enzyme inhibitors (ACEIs) than in a subgroup not treated with these drugs. In conclusion, this study has shown that increased myocardial expression of
CYP11B2 mRNA is associated with increased myocardial
fibrosis and with the severity of
left ventricular dysfunction in human CHF. In addition,
CYP11B2 expression and cardiac
fibrosis are found to be decreased in CHF patients on
drug therapy comprising
spironolactone combined with ACEIs.