Parathyroid Hormone-Related Protein Is Produced in the Myocardium and Increased in Patients with Congestive Heart Failure
Kazuhide Ogino,
Kazuyoshi Ogura,
Yoshiharu Kinugasa,
Yoshiyuki Furuse,
Kazuhiko Uchida,
Masaki Shimoyama,
Toru Kinugawa,
Shuichi Osaki,
Masahiko Kato,
Yoko Tomikura,
Osamu Igawa,
Ichiro Hisatome,
John P. Bilezikian and
Chiaki Shigemasa
Division of Cardiology, Department of Medicine, Faculty of Medicine, Tottori University (K.Ogi., K.Ogu., Y.K., Y.F., K.U., M.S., T.K., S.O., M.K., Y.T., O.I., I.H., C.S.), Yonago 683-8504, Japan; and Departments of Medicine and Pharmacology, Columbia University College of Physicians and Surgeons (J.P.B.), New York, New York 10032
Address all correspondence and requests for reprints to: Kazuhide Ogino, M.D., Ph.D., Division of Cardiology, Department of Medicine, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan. E-mail: k-ogino{at}umin.ac.jp.
Abstract
PTHrP is produced in a wide variety of different cells, includingcardiomyocytes. Its production is augmented by mechanical andneurohumoral stimulation, and PTHrP has positive chronotropicand vasodilatory effects. Thus, in the heart, PTHrP has thepotential to serve as a mechano-sensitive regulatory molecule.We evaluated peripheral and central levels of PTHrP in patientswith congestive heart failure (CHF) and tested the hypothesisthat PTHrP is released from the heart in patients with CHF.Intact full-length PTHrP (i-PTHrP) and C-terminal PTHrP (c-PTHrP)levels were measured in the plasma of 64 patients with CHF and12 controls. Plasma PTHrP concentrations in the coronary sinusand aortic root were also measured in 18 CHF patients and 10controls. Both plasma i-PTHrP and c-PTHrP levels in CHF patientswere significantly higher than control levels and increasedas a function of New York Heart Association classification.There were significant correlations between c-PTHrP levels andplasma norepinephrine, brain natriuretic peptide, angiotensinII, and endothelin-1 levels. Plasma i-PTHrP was significantlycorrelated with left ventricular ejection fraction and end-diastolicand end-systolic dimensions. Plasma i-PTHrP levels were significantlyhigher in the coronary sinus than in the aortic root in CHFpatients, but among controls concentrations of i-PTHrP wereindistinguishable at these two sites. This is the first reportdemonstrating that PTHrP is produced in the myocardium and isincreased in CHF; these findings suggest that PTHrPs levelsmight be modulated by cardiac performance in patients with CHF.
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