Abstract
Autosomal dominant mutations in myosin binding protein C (MYBPC3) account for up to 30% of myofibrillar mutations causing Hypertrophic Cardiomyopathy (HCM). We used SPontaneous Oscillatory Contractions (SPOC) to compare the performance of isolated cardiomyocytes from heterozygous MYBPC (þ/-) and homozygous MYBPC (-/-) and wild type (þ/þ) mice. Our aim is to identify changes in their contractile parameters. SPOC is a physiological state that is intermediate to full contraction and relaxation. The stable auto-oscillatory properties of SPOC are well suited to precise measurements of contraction and relaxation.
Preliminary evaluations reveal there is: (1) a progressive prolongation in both the relative lengthening and shortening periods from MYBPCþ/þ to MYBPCþ/- and MYBPC-/-; (2) MYBPCþ/- exhibits faster rates of lengthening than MYBPCþ/þ; (3) MYBPC-/- displays significantly depressed rates of shortening compared to MYBPCþ/- and MYBPCþ/þ. These findings suggest significant systolic dysfunction in MYBPC-/- associated with severe hypertrophic remodelling. Perhaps, more importantly MYBPCþ/- exhibits diastolic dysfunction consistent with previous reports examining SPOC in human HCM at the 56th Biophysical Society Meeting. We conclude that SPOC can objectively assess the functional state of heart muscle fibres in this mouse model.
Preliminary evaluations reveal there is: (1) a progressive prolongation in both the relative lengthening and shortening periods from MYBPCþ/þ to MYBPCþ/- and MYBPC-/-; (2) MYBPCþ/- exhibits faster rates of lengthening than MYBPCþ/þ; (3) MYBPC-/- displays significantly depressed rates of shortening compared to MYBPCþ/- and MYBPCþ/þ. These findings suggest significant systolic dysfunction in MYBPC-/- associated with severe hypertrophic remodelling. Perhaps, more importantly MYBPCþ/- exhibits diastolic dysfunction consistent with previous reports examining SPOC in human HCM at the 56th Biophysical Society Meeting. We conclude that SPOC can objectively assess the functional state of heart muscle fibres in this mouse model.
Original language | English |
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Article number | 1580-Pos |
Pages (from-to) | 309A-309A |
Number of pages | 1 |
Journal | Biophysical Journal |
Volume | 104 |
Issue number | 2 |
DOIs | |
Publication status | Published - 29 Jan 2013 |
Externally published | Yes |
Event | 57th Annual Meeting of the Biophysical-Society - Philadelphia, United States Duration: 2 Feb 2013 → 6 Feb 2013 |