Alterations in collagen cross-linking impair myocardial contractility in the mouse heart.
A number of genetic disorders in humans are associated with defects in the synthesis and metabolism of collagen, which are accompanied by multiple cardiovascular disease processes. To determine whether genetically determined cross-linking abnormalities of collagen may alter cardiac function, left ventricular papillary muscles of mice with a genetic defect in the cross-linking of collagen (Movbr) were studied in vitro. With respect to controls, increases in time to peak tension, from 102 +/- 1.4 to 125 +/- 5.4 msec (p less than 0.001), and time to one-half relaxation, from 76 +/- 3.0 to 98 +/- 6.1 msec (p less than 0.05), were measured. Moreover, resting tension at the length associated with maximum developed isometric force (L) was elevated, from 11.1 +/- 1.7 to 19.3 +/- 1.1 mN/mm2 (p less than 0.001), and a similar difference was also seen throughout the physiological range of muscle lengths. In contrast, developed tension was depressed at 93-97% of L. Peak rate of tension rise and decay were diminished whereas time to peak rate of tension rise was prolonged. Isotonically, a decrease in the magnitude of peak shortening at L, from 4.0 +/- 0.5 to 2.0 +/- 0.2% (p less than 0.04), and an increase in time to peak shortening, from 100 +/- 2.3 to 129 +/- 2.8 msec (p less than 0.001), were seen. In addition, peak velocities of shortening and relengthening were diminished in the Movbr mouse heart. In conclusion, the impairment in collagen cross-linking alters cardiac mechanics by a reduction in force-generating ability and a prolongation of the timing parameters of the systolic and diastolic phases of contraction in vitro.
Capasso
J M
JM
Department of Pathology, New York Medical College, Valhalla 10595.
Robinson
T F
TF
Anversa
P
P
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000502:physiology; D003094:Collagen / Q000502:physiology* / Q000648:ultrastructure; D006321:Heart / Q000033:anatomy & histology; D051379:Mice; D008817:Mice, Mutant Strains; D009200:Myocardial Contraction; D009929:Organ Size; D010210:Papillary Muscles / Q000033:anatomy & histology; D011485:Protein Binding
D003094:Collagen; D002118:Calcium