Novel markers of left ventricular hypertrophy in uremia.
OBJECTIVE
Left ventricular hypertrophy (LVH) is the most frequent cardiac complication in chronic renal disease. Previous studies implicate elevated serum phosphorus as a risk factor for LVH.


METHODS
We treated 5/6 nephrectomized rats with enalapril or enalapril + sevelamer carbonate for 4 months to determine if sevelamer carbonate had an additional beneficial effect on the development of LVH and uremia-induced left ventricle (LV) remodeling.


RESULTS
Uremia increased LV weight and cardiomyocyte size. Enalapril and enalapril + sevelamer blunted the increase in left ventricular weight. Only enalapril + sevelamer diminished the increase in cardiomyocyte size. Uremia increased cyclin D2 and PCNA and decreased p27 protein expression in the heart. Enalapril + sevelamer diminished the decrease in p27 expression caused by uremia. Uremia increased Ki67-positive and phosphohistone H(3)-positive interstitial cells. This was not seen in cardiomyocytes. Multivariable regression analysis showed that increased phosphorus was an independent risk factor for both increased LV weight and cardiomyocyte size.


CONCLUSIONS
These data suggest left ventricular remodeling consists of cardiomyocyte hypertrophy and interstitial cell proliferation, but not cardiomyocyte proliferation. p27 and cyclin D2 may play important roles in the development of LVH. In addition, phosphorus can be an independent risk factor for the development of LVH.
Nakamura
Hironori
H
Washington University Medical School, St. Louis, Mo., USA.
Tokumoto
Masanori
M
Mizobuchi
Masahide
M
Ritter
Cynthia S
CS
Finch
Jane L
JL
Mukai
Masanori
M
Slatopolsky
Eduardo
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000473:pathology; D011073:Polyamines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069603:Sevelamer; D014511:Uremia / Q000150:complications*
D000806:Angiotensin-Converting Enzyme Inhibitors; D018797:Cell Cycle Proteins; D011073:Polyamines; D004656:Enalapril; D000069603:Sevelamer