| First Author | Mencke R | Year | 2019 |
| Journal | Am J Pathol | Volume | 189 |
| Issue | 12 | Pages | 2503-2515 |
| PubMed ID | 31539519 | Mgi Jnum | J:283744 |
| Mgi Id | MGI:6388081 | Doi | 10.1016/j.ajpath.2019.08.006 |
| Citation | Mencke R, et al. (2019) Klotho Deficiency Induces Arteriolar Hyalinosis in a Trade-Off with Vascular Calcification. Am J Pathol 189(12):2503-2515 |
| abstractText | Hyalinosis is a vascular lesion affecting the renal vasculature and contributing to aging-related renal function decline. We assessed whether arteriolar hyalinosis is caused by Klotho deficiency, a state known to induce both renal and vascular phenotypes associated with aging. Histochemistry was used to assess hyalinosis in Klotho(-/-) kidneys, compared with Klotho(+/-) and wild-type littermates. Immunohistochemistry was used to investigate vascular lesion composition and the different layers of the vascular wall. Finally, spironolactone was used to inhibit calcification in kl/kl mice, and vascular lesions were characterized in the kidney. Arteriolar hyalinosis was detected in Klotho(-/-) mice, which was present up to the afferent arterioles. Hyalinosis was accompanied by loss of alpha-smooth muscle actin expression, whereas the endothelial lining was mostly intact. Hyalinous lesions were positive for IgM and iC3b/c/d, indicating subendothelial leakage of plasma proteins. The presence of extracellular matrix proteins suggested increased production by smooth muscle cells (SMCs). Finally, in Klotho(-/-) mice with marked vascular calcification, treatment with spironolactone allowed for replacement of calcification by hyalinosis. Klotho deficiency potentiates both endothelial hyperpermeability and SMC dedifferentiation. In the absence of a calcification-inducing stimulus, SMCs assume a synthetic phenotype in response to subendothelial leakage of plasma proteins. In the kidney, this results in arteriolar hyalinosis, which contributes to the decline in renal function. Klotho may play a role in preventing aging-related arteriolar hyalinosis. |
