Differences in extracellular matrix proteins between Friesian horses with aortic rupture, unaffected Friesians and Warmblood horses

Abstract

SummaryBackground: Unlike in Warmblood horses, aortic rupture is quite common in Friesian horses, in which a hereditary trait is suspected. The aortic connective tissue in affected Friesians shows histological changes such as medial necrosis, elastic fibre fragmentation, mucoid material accumulation and fibrosis with aberrant collagen morphology. However, ultrastructural examination of the collagen fibres of the mid-thoracic aorta has been inconclusive in further elucidating the pathogenesis of the disease. Objectives: To assess several extracellular matrix (ECM) components biochemically in order to explore a possible underlying breed-related systemic ECM defect in Friesians with aortic rupture. Study design: Cadaver study. Methods: Tissues from affected Friesians (n = 18), unaffected Friesians (n = 10) and Warmblood horses (n = 30) were compared. Samples were taken from the thoracic aorta at the level of the rupture site, from two locations caudal to the rupture and from the deep digital flexor tendon. Total collagen content, post-translational modifications of collagen formation including lysine hydroxylation, and hydroxylysylpyridinoline (HP), lysylpyridinoline (LP) and pyrrole cross-links were analysed. Additionally, elastin cross-links, glycosaminoglycan content and matrix metalloproteinase (MMP) activity were assessed. Results: Significantly increased MMP activity and increased LP and HP cross-linking, lysine hydroxylation and elastin cross-linking were found at the site of rupture in affected Friesians. These changes may reflect processes involved in healing and aneurysm formation. Unaffected Friesians had less lysine hydroxylation and pyrrole cross-linking within the tendons compared with Warmblood horses. No differences in the matrix of the aorta were found between normal Warmbloods and Friesian horses. Main limitations: Small sample size. Conclusions: The differences in collagen parameters in tendon tissue may reflect differences in connective tissue metabolism between Friesians and Warmblood horses.

Thoracic aortic rupture in horses

“…Collagen is central for tensile strength and elastin for elastic resilience [42]. There are important differences between Friesian horses and Warmblood horses [43]: lysine hydroxylation and pyrrole cross links, which are important collagen maturation markers, were significantly lower in deep digital flexor tendon of healthy Friesian horses than in Warmblood horses [43]. These findings suggest there are constitutive differences in connective tissue metabolism and homeostasis between Warmblood and Friesian horses.…”

Differences in ultrasound‐derived arterial wall stiffness parameters and noninvasive blood pressure between Friesian horses and Warmblood horses

“…Although the results found in our study did not indicate true hypertension, the continuously increased blood pressure in Friesians might lead to an increased amount of collagen in the Friesian aortic wall. Indeed, Friesians are known to have an increased amount of collagen in the tunica media of the aorta compared to Warmblood horses, in combination with a different collagen cross‐linking pattern . As previously shown, an oversized cuff will underestimate blood pressure, whereas using too small a cuff in relation to tail circumference will overestimate it .…”

“…Collagen is essential to prevent over‐stretching and rupture, whereas elastin is essential for stretching and recoil of the artery, in order to buffer differences in pressure between systole and diastole . Previous postmortem studies identified differences in composition and relative amounts of collagen and elastin between unaffected Friesian horses, affected Friesian horses and Warmblood horses, that might be related to the predisposition of Friesian horses to aortic rupture. Moreover medial necrosis is found at the site of rupture in affected Friesians, that might be related to connective tissue disorders, hypertension, ischemia, or inflammation .…”

Corneal cross‐linking as a treatment for corneal dystrophy with secondary bacterial infection in a Friesian horse

“…Collagen abnormalities have been described in other organs in Friesian horses. For example, increased matrix metalloproteinase activity, lysine hydroxylation and elastin cross‐linking were found at the site of aortic rupture in affected horses . Another study described disorganized elastin in the aorta of affected animals .…”

“…Additionally, the frequency of dehiscence of conjunctival grafts was high in Friesian horses with corneal dystrophy (5/9 eyes) with ongoing degenerative processes as presumed cause and a second anesthesia necessary in three out of five eyes . Alternatives to surgical interventions under general anesthesia would, therefore, be welcome, especially since these patients can represent an increased anesthetic risk as a result of associated cardiovascular disease …”