This Article Full Text Full Text (PDF) All Versions of this Article: 2/2/121    most recent CIRCHEARTFAILURE.108.813261v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mobine, H. R. Articles by Edelman, E. R. Search for Related Content PubMed PubMed Citation Articles by Mobine, H. R. Articles by Edelman, E. R. Related Collections Other heart failure Animal models of human disease Related Article

Original Articles

Pheochromocytoma-Induced Cardiomyopathy is Modulated by the Synergistic Effects of Cell-Secreted Factors

Hector R. Mobine, PhD; Aaron B. Baker, PhD; Libin Wang, MD, PhD; Hiroko Wakimoto, MD, PhD; Kurt C. Jacobsen, MS; Christine E. Seidman, MD; J.G. Seidman, PhD and Elazer R. Edelman, MD, PhD

From the Harvard-MIT Division of Health Sciences and Technology (H.R.M., A.B.B., E.R.E.), Massachusetts Institute of Technology, Cambridge, Mass; Department of Genetics (L.W., H.W., K.C.J., C.E.S., J.G.S.), Harvard Medical School; Howard Hughes Medical Institute (C.E.S.); and Cardiovascular Division (E.R.E.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Hector R. Mobine, ME, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E25-442, Cambridge, MA 02139. E-mail mobine{at}mit.edu

Received August 7, 2008; accepted November 20, 2008.

Background— Pheochromocytomas are rare tumors derived from the chromaffin cells of the adrenal medulla. Although these tumors have long been postulated to induce hypertension and cardiomyopathy through the hypersecretion of catecholamines, catecholamines alone may not fully explain the profound myocardial remodeling induced by these tumors. We sought to determine whether changes in myocardial function in pheochromocytoma-induced cardiomyopathy result solely from catecholamines secretion or from multiple pheochromocytoma-derived factors.

Methods and Results— Isolated cardiomyocytes incubated with pheochromocytoma-conditioned growth media contracted at a higher frequency than cardiomyocytes incubated with norepinephrine (NE) only. Sprague-Dawley rats and black-6 mice were implanted with agarose-encapsulated pheochromocytoma (PC12) cells, dihydroxyphenylalanine decarboxylase knock-out PC12 cells deficient in NE (PC12-KO), or NE-secreting pumps. PC12 cell implantation increased left ventricular dilation by 35±6% and 9.6±1.4% and reduced left ventricular fractional shortening by 20±3% and 28±4% in rats and mice compared with animals dosed only with NE, respectively. Elimination of NE secretion in PC12-KO cells induced neither cardiac dilation (3.9%±1.8% increase versus control) nor changes in (1.9%±0.4% reduction) fractional shortening compared to controls.

Conclusions— Pheochromocytomas induce a greater degree of cardiomyopathy than equivalent doses of NE, suggesting pheochromocytoma-induced cardiomyopathy is not solely mediated by NE, rather pheochromocytoma secretory factors in combination with catecholamines act synergistically to induce greater cardiac damage than catecholamines alone.

Key Words: norepinephrine • cardiomyopathy • catecholamines • heartfailure

---

 

CLINICAL PERSPECTIVE

Related Article

Pheochromocytoma-Induced Cardiomyopathy is Modulated by the Synergistic Effects of Cell-Secreted Factors

Hector R. Mobine, Aaron B. Baker, Libin Wang, Hiroko Wakimoto, Kurt C. Jacobsen, Christine E. Seidman, J.G. Seidman, and Elazer R. Edelman
Circ Heart Fail 2009 2: 121-128. [Abstract] [Full Text] [PDF]