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1 Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA; Department of Surgery, Division of Cardiothoracic Surgery, University of Illinois at Chicago, Chicago, IL, USA
2 Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA
3 Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA; Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
4 Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
5 Department of Surgery, Division of Cardiothoracic Surgery, University of Illinois at Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: pdetombe{at}uic.edu.
Diabetes mellitus (DM) is associated with a distinct cardiomyopathy. Whether cardiac myofilament function is altered in human DM is unknown. Accordingly, myocardial biopsies were obtained from 7 DM patients and 5 control, non-diabetic patients undergoing coronary artery bypass surgery. Myofilament function was assessed by determination of the developed force-[Ca2+] relationship in skinned cardiac cell derived from flash frozen human biopsies. Separate control experiments revealed that flash freezing of biopsy specimens did not affect myofilament function. All patients in the DM cohort were classified as type-2 DM and most showed signs of diastolic dysfunction. DM was associated with depressed myofilament function, that is, decreased calcium sensitivity (29%; p<0.05 vs. control) and a trend towards reduction of maximum Ca2+ saturated force (29%; p=0.08 vs control). The slope of the force-[Ca2+] relationship (Hill coefficient) was not affected by diabetes, however. We conclude that human diabetes mellitus is associated with decreased cardiac myofilament function. Depressed cardiac myofilament calcium responsiveness may underlie the depressed ventricular function characteristic of human diabetic cardiomyopathy.
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