IMMUNOINFLAMMATORY, DEGENERATIVE, NUTRITIONAL, TRAUMATIC, AND GENETIC DISEASES Vet Pathol 45:617–625 (2008) Arterial Calcification in Race Horses L. G. ARROYO, M. A. HAYES, J. DELAY, C. RAO, B. DUNCAN, AND L. VIEL Departments of Pathobiology (LGA, MAH), Clinical Studies (LV), Ontario Veterinary College, and Animal Health Laboratory (JD), University of Guelph, Guelph; Forensic Pathology Unit, Hamilton Health Science Campus, Department of Pathology and Molecular Medicine, McMaster University, Hamilton (CR). Ontario Racing Commission (BD), Toronto, Ontario, Canada Abstract. Calcification of large arteries has been sporadically reported in horses. The pathogenesis is still unknown, but recent studies in humans suggest that this is a regulated biomineralizing process. This study surveyed the prevalence, distribution, and severity of vascular calcification in Thoroughbred and Standardbred racehorses. Histopathologic, ultrastructural imaging, and energy dispersive X-ray elemental analyses were used to examine the lesions. Calcification of the tunica media, predominantly the pulmonary artery, was found in 82% of horses (83/101). Young adult horses (mean [SD] age in years, 4.44 6 2.17) of both breeds and sexes were similarly affected. Lesions appeared as white-to-yellowish, hard, and gritty plaques of variable size. On microscopic examination, elastic fibers within the tunica media were thinned, fragmented, and calcified, and surrounded by dense collagen matrix. Elemental analysis showed distinct peaks for calcium and phosphorus, consistent with hydroxyapatite mineral. The frequent occurrence of calcification in the tunica media of large pulmonary arteries of young racing horses indicates the need to investigate its pathogenesis and potential clinical implications. Key words: Arteries; calcification; electron microscopy; histology; horse; vascular diseases. Introduction Arterial calcification involves calcium mineral deposition along one or more layers of the arterial vessel wall. 15,20 It may occur in the tunica media of the artery (known as Mo ¨nckeberg’s sclerosis) and/or in the intima, where it is always associated with atherosclerosis in humans. 28 The pathogenesis of medial artery calcification in humans is still poorly understood, but it is hypothesized to result from a regulated biomineralization process that resembles embryonic osteogenesis, rather than as a passive response to degeneration. 6,10 Results of recent studies demonstrate that various proteins (i.e., alkaline phosphatase, osteocalcin, and collagen II) normally involved in bone mineralization are also present in calcified areas of the arterial wall. 28,33 Furthermore, vascular smooth-muscle cells may ultimately acquire potential biomineralizing capabilities by undergoing osteogenic and/or chondrogenic differentiation. 28 The structural and morphologic changes that occur with vascular calcification affect the elastic compli- ance of the arterial wall and cause vascular stiffness. 23 Arterial stiffness is a significant indepen- dent factor associated with organ dysfunction and increased risk for cardiovascular morbidity and mortality. 27,34 Calcification of large arterial vessels, such as aorta, pulmonary artery, pulmonary artery branch- es, and carotid arteries, has been reported in horses. 9,17,25 In an abattoir survey, Cranley 9 ob- served calcification of the pulmonary artery in nearly 27% of the Thoroughbred horses versus less than 6% in ponies and cobs. In humans, medial artery calcification usually occurs as a degenerative process that becomes more severe with age, whereas it has been reported in horses at a relatively early age (,5 years) and particularly in those with a racing background. 17 Nakamura et al. 25 found histologic abnormalities of the carotid artery in 30 of 64 Thoroughbred horses (2–4 years old) and in 3 of 13 Thoroughbred foals. The 617
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