Collagen Organization in Canine Myxomatous Mitral Valve Disease: An X-Ray Diffraction Study

Abstract

Collagen fibrils, a major component of mitral valve leaflets, play an important role in defining shape and providing mechanical strength and flexibility. Histopathological studies show that collagen fibrils undergo dramatic changes in the course of myxomatous mitral valve disease in both dogs and humans. However, little is known about the detailed organization of collagen in this disease. This study was designed to analyze and compare collagen fibril organization in healthy and lesional areas of myxomatous mitral valves of dogs, using synchrotron small-angle x-ray diffraction. The orientation, density, and alignment of collagen fibrils were mapped across six different valves. The findings reveal a preferred collagen alignment in the main body of the leaflets between two commissures. Qualitative and quantitative analysis of the data showed significant differences between affected and lesion-free areas in terms of collagen content, fibril alignment, and total tissue volume. Regression analysis of the amount of collagen compared to the total tissue content at each point revealed a significant relationship between these two parameters in lesion-free but not in affected areas. This is the first time this technique has been used to map collagen fibrils in cardiac tissue; the findings have important applications to human cardiology.

Active stiffening of mitral valve leaflets in the beating heart

“…MV leaflets have extensive passive collagen fiber networks (5,11,12,15,18), and the stress-strain relationship of isolated leaflets (3,14,22,27) is consistent with the material properties of passive collagen fibers. Our recent study (21), however, suggested that leaflet stiffness in the beating heart (slope of the leaflet stress-strain curve) was much greater than that of passive tissue, and studies of freshly isolated, oxygenated, stimulated leaflets in myographs (39) and in open hearts on cardiopulmonary bypass (CBP) (7,32) have suggested that the mechanical properties of MV leaflets may be altered actively.…”

Pathology, protein expression and signaling in myxomatous mitral valve degeneration: Comparison of dogs and humans

“…Unstable, immature and abnormally crosslinked collagen molecules were identified. 66,67 Furthermore, an accumulation of proteoglycans, lipids and hexosamines was detected in canine MMVD. 8,68,69 Immunohistochemical studies in mild canine MMVD showed an irregularly split basement membrane.…”

Pathology of myxomatous mitral valve disease in the dog

“…4,17,18,63 The anterior to posterior length ratio has been reported as 1.7 to 1, 38 The chordae tendineae and papillary muscles Effective closure of the mitral valve requires complex, temporal, and geometric coordination of the left atrioventricular annulus, mitral leaflets, and subvalvular apparatus. Each mitral valve leaflet is adjoined to the anterior or posterior papillary muscles or occasionally, directly to the ventricular wall by fibrous chords, the chordae tendineae.…”