Periostin: A possible treatment for heart failure. July 20, 2007
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Periostin: A possible treatment for heart failure
July 20, 2007 by JoEllyn Abraham, MD
Exciting new research led by Bernhard Kuhn, MD in the Department of Cardiology at Children's Hospital Boston, suggests a novel mechanism for treatment of the failing heart.kuhnref1 Building on the work of Judith LitvinLitvinref1 and Naruto KatsuragiKatsuragiref1, Dr. Kuhn and his colleagues at Massachusetts General Hospital and the Mount Sinai School of Medicine became interested in a component of the extracellular matrix called periostin that is known to be present both during cardiac development and at times of myocardial injury.
At a cellular level, myocardial infarction leads to apoptosis of the affected cardiomyocytes and eventual scar formation. Although some research has shown that mature cardiomyocytes are capable of reentering the cell cycle, the percentage that actually increase their cell-cycle activity after a myocardial infarction (0.004%)soonpaaref1 is not sufficient for cardiac regeneration.
To determine whether periostin could increase cardiomyocyte proliferation when delivered through the cardiac extracellular matrix, recombinant periostin was injected into the myocardium of rats (N= 4). Control rats were injected with fibronectin (N=5) or buffer (N=3). BrdU was injected into the peritoneum to detect the portion of cycling cardiomyocytes. After 7 days, periostin induced cytokinesis in 0.1 +/- 0.03% (p<0.05) and DNA synthesis in 0.7+/- 0.1% (p<0.01) of cardiomyocyte nuclei was detected in the injected area of the periostin-injected rats, compared to virtually no activity in the control rats.
Periostin was also found to both improve cardiac function after myocardial infarction and reduce fibrosis and hypertrophy. Gelfoam patches loaded with periostin or with buffer were administered to the epicardium of rats at the time of myocardial infarction. Echocardiography was performed at both 1 and 12 weeks. Shortening fraction, ejection fraction and end-diastolic dimension were calculated. Improved left ventricular remodeling was seen across all three paramenters in the periostin-treated rats: increased shortening fraction, increased ejection fraction and smaller left ventricular end-diastolic dimension. The periostin-treated rats were also found to have a smaller scar volume, a thicker left ventricular free wall and a thinner septum. Interestingly, the 12-week periostin-treated rat myocytes had a 1.5-fold increase in arteriolar density as compared to controls. These findings all point toward favorable left ventricular remodeling.
It remains to be seen whether this research could be translated into a safe and effective intervention for human patients after myocardial infarction or in the context of heart failure of any etiology. However, the authors are hopeful that “stimulating proliferation of endogenous cardiomyocytes with periostin, periostin derivatives, or mimetics may provide an innovative approach to induce myocardial repair.”kuhnref1
References
- kuhnref1 PMID 17632525
- Litvinref1 PMID 16414453
- Katsuragiref1 PMID 15381649
- soonpaaref1 PMID 9670914
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Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
