Challenging Friesian horse diseases: aortic rupture and megaesophagus

Abstract

Aortic rupture is quite rare in Warmblood horses and is best known as an acute and fatal rupture of the aortic root in older breeding stallions. It has now become clear that aortic rupture, which is diagnosed around an age of 4 years, is more frequent in the Friesian breed than in others. The high prevalence in Friesians may be due to increased genetic susceptibility Whereas Friesian horses with aortic rupture may develop acute forms, the majority of Friesians will display a subacute or chronic disease process. Friesians with a chronic form may show clinical signs, such as recidivating peripheral oedema, jugular pulsation or a strong bounding pulsation in the carotid artery, in the weeks to months prior to death. In Friesian horses the aortic rupture is encountered at the level of the aortic arch near the ligamentum arteriosum, which is more caudally than seen in Warmblood horses. Several cases showed presence of a longitudinal dissection of the aortic wall. A few Friesians with aortic rupture developed a circumferential cuff of blood around the aorta. All cases with chronic lesions in the aortic wall had an aorto-pulmonary fistulation in combination with a pseudoaneurysm. Factors that may interfere with the location of rupture in Friesians are genetic disorders, connective tissue disorders affecting the vessel wall integrity, geometrical abnormalities including wall thickness, lumen diameter and abnormal blood pressure. Histological features at the site of aortic rupture in Friesian horses are medial necrosis, disorganization and fragmentation of elastic laminae, aortic medial smooth muscle hypertrophy and accumulation of mucoid material. Biochemical analysis of the aortic wall in Friesian horses revealed increased MMP activity at the level of aortic rupture. Furthermore, the elastin cross-links desmosine and isodesmosine were increased, probably due to the remodeling and healing process at the site of rupture. Several biochemical differences between Friesians and Warmblood horses were demonstrated, including differences in the post-translational modifications of collagen in tendons and of GAG content in aorta and tendon tissue. Differences or changes in the ECM of the aorta of affected Friesians may have effects on the stiffness and strength of the aortic wall, and may also interfere with cell-matrix interactions and signaling cascades which are important for maintenance of the mechanical properties of the ECM. Clinically a high number of Friesians is suffering from megaesophagus (prevalence 2.2%), of which the majority is younger than 5 years. Morphological abnormalities were seen in the esophageal wall of young Friesians characterized by increased deposition of disorganized collagen and a decrease in elastin. These changes were present in the dilated but also in the non-dilated parts of the esophagus and were similar to those found in the aortic wall of Friesians with aortic rupture and aortopulmonary fistulation. Together, these findings are supportive of a systemic connective tissue disorder as underlying cause. Given the narrow genetic base of the Friesian breed and the significant differences found in extracellular matrix composition and metabolism between Friesians and warmbloods, a contribution of genetic factors to both Friesian disorders is likely.