Abstract
Background
Tendinous xanthomas associated with heritable hyperlipidemia are clinically well known. Nevertheless, there have been few basic investigations of the pathogenesis of these xanthomas. To clarify the pathogenesis of these xanthomas, we examined the localization and histopathological features of xanthomatous tissues in the extremities of Watanabe heritable hyperlipidemic (WHHL) rabbits.
Methods
Twenty-six WHHL rabbits at 1–31 months of age were dissected to observe the localization of xanthomas. In the histopathological study, tendons and ligaments that included xanthomatous tissues were sectioned and stained with hematoxylin and eosin, Masson's trichrome, and toluidine blue. Immunohistochemical staining was performed with RAM-11, a monoclonal antibody specific for rabbit macrophages, and CD31, a monoclonal antibody specific for endothelial cells.
Results
At necropsy examination, spontaneous development of xanthomas was observed in the plantar side of the plantaris tendon, the flexor retinaculum of the carpus, and around the digital flexor tendons of each joint level. Xanthoma formation was observed from 10 months of age and progressed with advancing age. The histomorphological study revealed that xanthomas had developed in superficial paratenon of the tendons that wrap around bony or fibrous pulleys. Many fibrocartilage cells were observed in the deep side of affected tendons. A large number of blood vessels were seen in the xanthomatous tissues of these WHHL rabbits. Immunohistochemical evaluation revealed that the xanthoma plaques contained endothelial cells and macrophages.
Conclusions
It is likely that mechanical stress and extensive vascularization are essential factors for xanthoma formation. Moreover, endothelial cells and macrophages cells are principal contributors to the pathogenesis of tendinous xanthomas and to atherogenesis.
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References
Y Watanabe (1980) ArticleTitleSerial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit), incidence and development of atherosclerosis and xanthoma Atherosclerosis 36 261–8 10.1016/0021-9150(80)90234-8 Occurrence Handle10.1016/0021-9150(80)90234-8 Occurrence Handle1:CAS:528:DyaL3cXksVeisbo%3D Occurrence Handle7406953
MS Brown JL Goldstein (1976) ArticleTitleFamilial hypercholesterolemia: a genetic defect in the low-density lipoprotein receptor N Engl J Med 294 1386–90 Occurrence Handle1:CAS:528:DyaE28Xks1Srur8%3D Occurrence Handle177875 Occurrence Handle10.1056/NEJM197604152941602
T Ito M Shiomi (2001) ArticleTitleCerebral atherosclerosis occurs spontaneously in homozygous WHHL rabbits Atherosclerosis 156 57–66 10.1016/S0021-9150(00)00622-5 Occurrence Handle10.1016/S0021-9150(00)00622-5 Occurrence Handle1:CAS:528:DC%2BD3MXjtlCitbk%3D Occurrence Handle11368997
M Shiomi T Ito S Yamada S Kawashima J Fan (2003) ArticleTitleDevelopment of an animal model for spontaneous myocardial infarction (WHHLMI rabbit) Arterioscler Thromb Vasc Biol 23 1239–44 Occurrence Handle10.1161/01.ATV.0000075947.28567.50 Occurrence Handle1:CAS:528:DC%2BD3sXltVGku74%3D Occurrence Handle12738683
M Shiomi T Ito Y Watanabe Y Tsujita M Kuroda M Arai et al. (1990) ArticleTitleSuppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low: effect of pravastatin sodium in combination with cholestyramine Atherosclerosis 83 69–80 10.1016/0021-9150(90)90132-3 Occurrence Handle10.1016/0021-9150(90)90132-3 Occurrence Handle1:CAS:528:DyaK3cXls1Ght74%3D Occurrence Handle2117930
M Valeo P Dalla Vedova L Di Giorgio AG Scarno A Giuliante (1996) ArticleTitleThe conservative treatment of xanthoma of the Achilles tendon in patients affected with type IIA hypercholesterolemia Chir Organi Mov 81 303–10 Occurrence Handle1:STN:280:DyaK2s7mt1Chug%3D%3D Occurrence Handle9009414
JJ Fahey HH Stark WF Donovan DB Drennan (1973) ArticleTitleXanthoma of the Achilles tendon: seven cases with familial hyperbetalipoproteinemia J Bone Joint Surg Am 55 1197–211 Occurrence Handle1:STN:280:DyaE2c%2FktlKqsw%3D%3D Occurrence Handle4758034
E Karaharju P Paavolainen T Holmstrom T Nikkari (1981) ArticleTitleXanthomas of the Achilles tendon Ann Chir Gynaecol 70 116–9 Occurrence Handle1:STN:280:DyaL387htF2qtA%3D%3D Occurrence Handle7325578
DE Marcinko II Miller JM Read SuffixIII (1984) ArticleTitleAchilles tendon hypercholesteremic xanthoma J Foot Surg 23 398–401 Occurrence Handle1:STN:280:DyaL2M%2Fls1SitA%3D%3D Occurrence Handle6501800
T Tomita T Ochi H Fushimi Y Matsuzawa K Ono (1994) ArticleTitleReconstruction of the Achilles tendon xanthoma: findings at operative re-exploration: a case report J Bone Joint Surg Am 76 444–7 Occurrence Handle1:STN:280:DyaK2c7ntFyltw%3D%3D Occurrence Handle8126051
MB Davies AJC Kuhrt MA Hakmi TWD Smith (2002) ArticleTitleRecurrent xanthoma of the tendo-Achilles Foot 12 166–70 10.1054/foot.2002.0731 Occurrence Handle10.1054/foot.2002.0731
CK Lee AB Weiss (1980) ArticleTitleXanthomas of the Achilles tendons: a case report of bilateral total resection and tendon reconstruction using the fascia lata J Bone Joint Surg Am 62 666–9 Occurrence Handle1:STN:280:DyaL3c3gsVCjsg%3D%3D Occurrence Handle7380866
SK Saraf SV Sharma (1992) ArticleTitleReconstruction for xanthoma of the Achilles tendon Int Orthop 16 37–8 10.1007/BF00182982 Occurrence Handle10.1007/BF00182982 Occurrence Handle1:STN:280:DyaK383kt1Snsw%3D%3D Occurrence Handle1572768
M Benjamin S Qin JR Ralphs (1995) ArticleTitleFibrocartilage associated with human tendons and their pulleys J Anat 187 625–33 Occurrence Handle8586561
M Benjamin JR Ralphs (1998) ArticleTitleFibrocartilage in tendons and ligaments — an adaptation to compressive load J Anat 193 481–94 10.1046/j.1469-7580.1998.19340481.x Occurrence Handle10.1046/j.1469-7580.1998.19340481.x Occurrence Handle10029181
M Benjamin EJ Evans (1990) ArticleTitleFibrocartilage J Anat 171 1–15 Occurrence Handle1:STN:280:DyaK3M7osFWntw%3D%3D Occurrence Handle2081696
R Ross (1993) ArticleTitleThe pathogenesis of atherosclerosis: a perspective for the 1990s Nature 362 801–9 10.1038/362801a0 Occurrence Handle10.1038/362801a0 Occurrence Handle1:CAS:528:DyaK3sXktVGqu7c%3D Occurrence Handle8479518
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Nakano, A., Kinoshita, M., Okuda, R. et al. Pathogenesis of tendinous xanthoma: histopathological study of the extremities of Watanabe heritable hyperlipidemic rabbits. J Orthop Sci 11, 75–80 (2006). https://doi.org/10.1007/s00776-005-0976-7
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DOI: https://doi.org/10.1007/s00776-005-0976-7