Aldosterone synthase (CYP11B2) expression and myocardial fibrosis in the failing human heart.
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.
Satoh
Mamoru
M
Second Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Nakamura
Motoyuki
M
Saitoh
Hidenori
H
Satoh
Hidetoshi
H
Akatsu
Tomonari
T
Iwasaka
Junji
J
Masuda
Tomoyuki
T
Hiramori
Katsuhiko
K
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003094:Collagen / Q000032:analysis; D019405:Cytochrome P-450 CYP11B2 / Q000096:biosynthesis* / Q000235:genetics; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004719:Endomyocardial Fibrosis / Q000201:enzymology* / Q000209:etiology; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013148:Spironolactone / Q000627:therapeutic use; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis / Q000235:genetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D012333:RNA, Messenger; D013148:Spironolactone; D003094:Collagen; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase