Mencke, R. (Rik) (2012) Klotho is not expressed endogenously in atherosclerotic vascular tissue. thesis, Medicine.
Full text available on request.Abstract
Background: Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). CVD in CKD patients is characterised by atherosclerosis, in which vascular smooth muscle cell (VSMC) dedifferentiation plays an important role. CKD patients have remarkably low levels of the anti-ageing hormone Klotho. Many phenotypic similarities exist between CKD patients and Klotho-deficient mice, such as a short lifespan, high levels of Fibroblast Growth Factor (FGF) 23, hyperphosphataemia, and marked atherosclerosis. Therefore, Klotho is a promising target protein for diagnostic and, possibly, for therapeutic purposes. It is unknown whether the association of Klotho deficiency and atherosclerosis is causal in nature and whether Klotho is endogenously expressed in the vasculature. Aim: To determine whether Klotho is expressed in vascular tissue and whether Klotho, endogenously expressed or exogenously derived, can inhibit vascular smooth muscle cell dedifferentiation. Methods: We used validated methods, including immunohistochemistry, Western blotting, and qRT-PCR, to assess Klotho expression in CKD and non-CKD plaques, healthy vascular tissue, and cultured VSMCs. We used collagen gel contraction assays under different experimental conditions to assess VSMC contractile function, which reflects differentiation. Results: We could not detect Klotho expression in any type of vascular tissue. However, we could not find an effect of Klotho on VSMC dedifferentiation either. Discussion/conclusion: We conclude that Klotho is not endogenously expressed in blood vessels. We have also not observed an effect of exogenous Klotho on VSMC differentiation, but a possible effect cannot be ruled out based on the present study.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor: and Hillebrands, Prof. dr. J.L. and Department of Pathology and Medical Biology, UMCG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:56 |
| Last Modified: | 25 Jun 2020 10:56 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1712 |
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