Alterations to myofibrillar protein function in nonischemic regions of the heart early after myocardial infarction.
Remote-zone left ventricular dysfunction (LVD) contributes to global reductions in contractile function after localized myocardial infarction (MI). However, the molecular mechanisms underlying this form of LVD are not clear. This study tested the hypothesis that myofibrillar protein function is directly affected in remote-zone LVD early after MI. Cardiac myosin and native thin filaments were purified from mouse myocardium taken from both the nonnecrotic zone adjacent to and the nonischemic zone remote from an infarct induced by 1 h of coronary occlusion followed by 24 h of reperfusion. Thin filament velocities were measured using the in vitro motility assay. Results showed that overall function was significantly reduced in samples from both the adjacent (43 +/- 12% of control, n = 7) and remote (53 +/- 8% of control, n = 13) zones when compared with control proteins (P < 0.05). Myosin from the remote zone propelled control thin filaments at reduced velocities similar to those measured above. In contrast, the Ca(2+) sensitivity of remote-zone thin filaments over control myosin was unchanged from control thin filaments (half-maximal at pCa 6.32 +/- 0.08 and 6.27 +/- 0.06, respectively) but showed a 20% increase in velocity at saturating Ca(2+) that parallels an increase in tropomyosin phosphorylation. Myosin dysfunction may be related to oxidation of cysteines in the myosin heavy chains or carbonylation of myosin binding protein-C. We hypothesize that phosphorylation of tropomyosin may serve a compensatory role, augmenting contraction during periods of oxidative stress when myosin function is compromised.
Rao
Vijay S
VS
Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, VA 22908, USA.
La Bonte
Laura R
LR
Xu
Yaqin
Y
Yang
Zequan
Z
French
Brent A
BA
Guilford
William H
WH
D000222:Adaptation, Physiological; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D009210:Myofibrils / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism*; D013314:Stress, Mechanical; D014018:Tissue Distribution; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
D020409:Molecular Motor Proteins; D009218:Myosins