1. Myosin Cross-Bridge Dynamics in Patients With Hypertension and Concentric Left Ventricular RemodelingClinical Perspective
by Cameron Donaldson, Bradley M. Palmer, Michael Zile, David W. Maughan, John S. Ikonomidis, Henk Granzier, Markus Meyer, Peter VanBuren, and Martin M. LeWinter
Circ Heart Fail
Volume 5(6):
November 20, 2012
Copyright © American Heart Association, Inc. All rights reserved.

2. Tension–pCa relationships.
Tension–pCa relationships. A, Passive tension under butanedione monoxime (BDM) conditions at 2.2 μm sarcomere length was greater in hypertension (HTN) compared with controls. Calcium-dependent tension development was reduced in the HTN group compared with controls at calcium concentrations at pCa ≤6. B, Thin filament sensitivity to calcium activation, presented here using normalized tension, was indistinguishable between the 2 groups. *P<0.05.
Cameron Donaldson et al. Circ Heart Fail. 2012;5:
Copyright © American Heart Association, Inc. All rights reserved.

3. A, B, Viscoelastic mechanics under relaxed conditions.
A, B, Viscoelastic mechanics under relaxed conditions. Under conditions of pCa 8 and 30 mmol/L butanedione monoxime (BDM), the elastic and viscous moduli were similar between coronary artery disease (A) and hypertension (HTN) (B). Upon removal of BDM, viscoelastic characteristics demonstrated the signature mechanical characteristics (ie, dips and shoulders) because of myosin cross-bridge formation in both groups. C, D, Skinning and storage procedures did not result in detectable levels of cardiac troponin I (cTnI) (C) or tropomyosin cTm (D) by Western blot analysis, which verifies that these procedures do not result in significant loss of thin filament regulation. The skinning solution with 400 mmol/L KCl provided a positive control.
Cameron Donaldson et al. Circ Heart Fail. 2012;5:
Copyright © American Heart Association, Inc. All rights reserved.

4. Myosin cross-bridge attachment time (ton) and stiffness.
Myosin cross-bridge attachment time (ton) and stiffness. A, Mean ton, was calculated as the reciprocal of 2πc and was significantly prolonged in hypertension (HTN) compared with controls at lower calcium concentrations. *P<0.05 B, Prolonged ton in HTN at pCa 8 underlies the lower frequencies at which the dips and shoulders of the viscoelastic characteristics occur. BDM indicates butanedione monoxime.
Cameron Donaldson et al. Circ Heart Fail. 2012;5:
Copyright © American Heart Association, Inc. All rights reserved.

5. Myosin cross-bridge viscoelastic stiffness measured under rigor conditions, that is, with all myosin cross-bridges formed and without MgATP to facilitate detachment, was significantly lower in hypertension (HTN) compared with controls.
Myosin cross-bridge viscoelastic stiffness measured under rigor conditions, that is, with all myosin cross-bridges formed and without MgATP to facilitate detachment, was significantly lower in hypertension (HTN) compared with controls. The moduli under butanedione monoxime (BDM) conditions were subtracted to demonstrate cross-bridge-dependent viscoelastic properties.
Cameron Donaldson et al. Circ Heart Fail. 2012;5:
Copyright © American Heart Association, Inc. All rights reserved.

6. Relative phosphorylation of myosin binding protein C (MyBPC) and troponin I (TnI).
Relative phosphorylation of myosin binding protein C (MyBPC) and troponin I (TnI). A, Phosphorylation of MyBPC and TnI was detected by ProQ diamond phosphostain compared with Coomassie Blue stain for protein density. B, Relative phosphorylation of MyBPC and TnI was reduced in myocardium of HTN patients (n=6) compared with controls (n=5). *P<0.05. BDM indicates butanedione monoxime.
Cameron Donaldson et al. Circ Heart Fail. 2012;5:
Copyright © American Heart Association, Inc. All rights reserved.

7. Model parameters of cross-bridge-dependent viscoelasticity.
Model parameters of cross-bridge-dependent viscoelasticity. A–C, Magnitudes of processes (A, B, and C) in mN/mm2 are proportional to myosin cross-bridge number, duty ratio, and stiffness. These magnitudes rise with calcium activation, less so in hypertension (HTN) compared with controls. *P<0.05; #P<0.01. D, Parameter k reflects the degree of elastic (k→0) vs viscous (k→1) response and was not significantly different between the groups. E, 2πb, representing the forward and reverse rate of myosin isomerization, was not different between the groups. F, The myosin detachment rate, 2πc, was significantly lower in HTN compared with controls at low calcium concentrations, that is, pCa >6.25. *P<0.05.
Cameron Donaldson et al. Circ Heart Fail. 2012;5:
Copyright © American Heart Association, Inc. All rights reserved.