Acute and specific collagen type I degradation increases diastolic and developed tension in perfused rat papillary muscle

Abstract

Collagen degradation is suggested to be responsible for long-term contractile dysfunction in different cardiomyopathies, but the effects of acute and specific collagen type I removal (main type in the heart muscle) on tension have not been studied. We determined the diastolic and developed tension length relations in isometric contracting perfused rat papillary muscles (perfusion pressure 60 cmH(2)O) before and after acute and specific removal of small collagen struts with the use of purified collagenase type I. At 95% of the maximal length (95%L(max)), diastolic tension increased 20.4 +/- 8.1% (P < 0.05, n = 6) and developed tension increased 15.0 +/- 6.7% after collagenase treatment compared with time controls. Treatment increased the diastolic muscle diameter by 7.1 +/- 3.4% at 95%L(max), whereas the change in diameter due to contraction was not changed. Diastolic coronary flow and normalized coronary arterial flow impediment did not change after collagenase treatment. Electron microscopy revealed that the number of small collagen struts, interconnecting myocytes, and capillaries was reduced to approximately 32% after treatment. We conclude that removal of the small collagen struts by acute and specific collagen type I degradation increases diastolic and developed tension in perfused papillary muscle. We suggest that diastolic tension is increased due to edema, whereas developed tension is increased because the removal of the struts poses a lower lateral load on the cardiac myocytes, allowing more myocyte thickening.

The relationship between myocardial extracellular matrix remodeling and ventricular function☆

“…This decrease in collagen in the papillary muscles was accompanied by a marked decrease in systolic function (i.e., reduced amount and rate of shortening, reflected by developed tension (T) and +dT/dt) without affecting isolated cardiomyocyte contractility, leading the authors to conclude that myocardial fibrillar collagen is a major contributor to normal myocardial systolic performance. In contrast to these findings, Lamberts et al [58] reported myocardial function was improved following specific degradation of collagen type I (i.e., an increase in developed tension and the rate of relaxation). Unfortunately, relaxation rates were not reported in the Baicu study, precluding comparison of this parameter.…”

Fibronectin increases the force production of mouse papillary muscles via α5β1 integrin

“…Rueckschloss et al [23] have reported that soluble FN enhanced Ca 2+ current in cardiomyocytes while soluble RGD peptide did not have any effect on Ca 2+ current. Lamberts et al used a specific type 1 collagenase enzyme and observed an increase in diastolic and developed tension [61]. Laminin binding to β1 integrins modulates Ca L through signaling pathways linked to adrenergic and cholinergic receptors signaling in cat atrial myocytes [62, 63].…”

What Mechanisms Underlie Diastolic Dysfunction in Heart Failure?

“…85 Digestion of purely endomysial fibers has the opposite effect. 86,87 Recent studies have begun targeting signaling factors to fibrosis, including transforming growth factor-␤, 88 the sodium-hydrogen exchanger, 89 angiotensin II receptor-mediated signaling, 90 and chymase, 91 correlating changes in collagen/fibrosis to chamber stiffening. Other studies have degraded collagen in normal and pressureload hypertrophied papillary muscles with plasmin 92 or oxidized glutathione and hydroxyproline, 93 and inhibited collagen cross-links with ␤-aminopropionitrile.…”