Hyaline Arteriolosclerosis in 30 Strains of Aged Inbred Mice

Abstract

During a screen for vascular phenotypes in aged laboratory mice, a unique discrete phenotype of hyaline arteriolosclerosis of the intertubular arteries and arterioles of the testes was identified in several inbred strains. Lesions were limited to the testes, and did not occur as part of any renal, systemic, or pulmonary arteriopathy or vasculitis phenotype. There was no evidence of systemic or pulmonary hypertension, and lesions did not occur in female ovaries. Frequency was highest in males of the SM/J (27/30, 90%) and WSB/EiJ (19/26, 73%) strains, aged 383 to 847 days. Lesions were sporadically present in males from several other inbred strains at a much lower (<20%) frequency. The risk of testicular hyaline arteriolosclerosis is at least partially underpinned by a genetic predisposition which is not associated with other vascular lesions (including vasculitis), separating out the etiology of this form and site of arteriolosclerosis from other related conditions that often co-occur in other strains of mice and in humans. Because of their genetic uniformity and controlled dietary and environmental conditions, mice are an excellent model to dissect the pathogenesis of human disease conditions. In this study a discrete genetically driven phenotype of testicular hyaline arteriolosclerosis in aging mice was identified. These observations open the possibility of identifying the underlying genetic variant(s) associated with the predisposition and therefore allowing future interrogation of the pathogenesis of this condition. AbstractDuring a screen for vascular phenotypes in aged laboratory mice, a unique discrete phenotype of hyaline arteriolosclerosis of the intertubular arteries and arterioles of the testes was identified in several inbred strains. Lesions were limited to the testes, and did not occur as part of any renal, systemic, or pulmonary arteriopathy or vasculitis phenotype. There was no evidence of systemic or pulmonary hypertension, and lesions did not occur in female ovaries. Frequency was highest in males of the SM/J (27/30, 90%) and WSB/EiJ (19/26, 73%) strains, aged 383 to 847 days. Lesions were sporadically present in males from several other inbred strains at a much lower (<20%) frequency. The risk of testicular hyaline arteriolosclerosis is at least partially underpinned by a genetic predisposition which is not associated with other vascular lesions (including vasculitis), separating out the etiology of this form and site of arteriolosclerosis from other related conditions that often co-occur in other strains of mice and in humans. Because of their genetic uniformity and controlled dietary and environmental conditions, mice are an excellent model to dissect the pathogenesis of human disease conditions. In this study a discrete genetically driven phenotype of testicular hyaline arteriolosclerosis in aging mice was identified. These observations open the possibility of identifying the underlying genetic variant(s) associated with the predisposition and therefore allowing future interrogation of the...

Raman spectroscopy reveals collagen and phospholipids as major components of hyalinosis in the arteriolosclerotic ulcer of Martorell

“…The presence of collagen has previously been described in hyaline arteriolosclerosis of intertubular arteries and arterioles in the testes of mice using Masson trichrome staining. 27 An increase in collagen type III and IV was also found in hyalinized glomeruli of patients with hypertensive nephrosclerosis through immunohistochemical staining and in situ hybridization. 42 Our results confirmed the crucial role of collagen in hyaline arteriolosclerosis and demonstrated its presence in the media of affected arterioles of hypertensive ischaemic skin ulcers and hypertensive nephropathy.…”

“…8,9,11,14,40,41 Although several authors have previously reported on these hyaline wall changes, which can typically be found in the media of arterioles and small arteries, 9,20,28 few attempts have been made to characterize these deposits. 27 We introduced Raman imaging as an important tool to reveal molecular changes at the micron level within the vascular wall and hyaline deposits. Our data analysis showed that subendothelial hyaline deposits were mainly composed of collagen and phospholipids, particularly phosphatidylcholine.…”

“…Arterioles show massive thickening of the vessel wall, leaving a narrow lumen that is often occluded, entailing local ischaemic injury, which can manifest in ischaemic skin infarction, such as in ASUM, or a decline in renal function, which is evident in hypertensive nephrosclerosis 8,9,11,14,40,41 . Although several authors have previously reported on these hyaline wall changes, which can typically be found in the media of arterioles and small arteries, 9,20,28 few attempts have been made to characterize these deposits 27 . We introduced Raman imaging as an important tool to reveal molecular changes at the micron level within the vascular wall and hyaline deposits.…”

“…23,24 Additionally, hyaline arteriolosclerosis can also be found in diabetic nephropathy or renal transplant recipients receiving calcineurin inhibitors. 20,[25][26][27] It has also been described in diabetic retinopathy, placental blood vessels of hypertensive women and subcortical arteriosclerotic encephalopathy. [17][18][19] Although several authors have previously reported on hyaline changes in hypertensive arteriopathies, 9,20,28 so far, only scarce information is available regarding the actual molecular composition of the hyaline wall depositions.…”

“…Vascular hyalinosis has been shown to be negatively correlated with eGFR levels and renal function outcomes and is a potential surrogate marker for interstitial hypoxia 23,24 . Additionally, hyaline arteriolosclerosis can also be found in diabetic nephropathy or renal transplant recipients receiving calcineurin inhibitors 20,25–27 . It has also been described in diabetic retinopathy, placental blood vessels of hypertensive women and subcortical arteriosclerotic encephalopathy 17–19 …”