BACKGROUND: Bone matrix proteins are expressed in calcified arteries from dialysis patients, suggesting that vascular smooth muscle cells (VSMCs) may transform to osteoblast-like cells. One of the key transcriptional regulators of osteoblast differentiation is Cbfa1. Thus, we hypothesized that this may be a key factor in arterial calcification. METHODS: To test this hypothesis, we examined sections of the inferior epigastric artery from uremic patients for the presence of Cbfa1 and type I collagen and osteopontin by in situ hybridization and immunostaining. We also examined the effect of pooled uremic sera from dialysis patients on the expression of Cbfa1 by reverse transcription-polymerase chain reaction (RT-PCR) in bovine VSMCs in vitro. RESULTS: Cbfa1 and osteopontin were expressed in both the media and the intima in vessels that were calcified, but there was only minimal staining in non-calcified vessels. In vitro studies demonstrated that pooled uremic serum, compared to pooled control human serum induced the expression of Cbfa1 by RT-PCR in bovine VSMCs in a time-dependent, nonphosphorus-mediated mechanism. CONCLUSION: These results support that Cbfa1 is a key regulatory factor in the vascular calcification observed in dialysis patients and is up-regulated in response to many uremic toxins.
BACKGROUND: Bone matrix proteins are expressed in calcified arteries from dialysis patients, suggesting that vascular smooth muscle cells (VSMCs) may transform to osteoblast-like cells. One of the key transcriptional regulators of osteoblast differentiation is Cbfa1. Thus, we hypothesized that this may be a key factor in arterial calcification. METHODS: To test this hypothesis, we examined sections of the inferior epigastric artery from uremic patients for the presence of Cbfa1 and type I collagen and osteopontin by in situ hybridization and immunostaining. We also examined the effect of pooled uremic sera from dialysis patients on the expression of Cbfa1 by reverse transcription-polymerase chain reaction (RT-PCR) in bovine VSMCs in vitro. RESULTS:Cbfa1 and osteopontin were expressed in both the media and the intima in vessels that were calcified, but there was only minimal staining in non-calcified vessels. In vitro studies demonstrated that pooled uremic serum, compared to pooled control human serum induced the expression of Cbfa1 by RT-PCR in bovine VSMCs in a time-dependent, nonphosphorus-mediated mechanism. CONCLUSION: These results support that Cbfa1 is a key regulatory factor in the vascular calcification observed in dialysis patients and is up-regulated in response to many uremic toxins.
Authors: Zheng Qin; Ruoxi Liao; Yuqin Xiong; Luojia Jiang; Jiameng Li; Liya Wang; Mei Han; Si Sun; Jiwen Geng; Qinbo Yang; Zhuyun Zhang; Yupei Li; Heyue Du; Baihai Su Journal: Ann Transl Med Date: 2021-04
Authors: Natalie A van Venrooij; Renata C Pereira; Yin Tintut; Michael C Fishbein; Navdeep Tumber; Linda L Demer; Isidro B Salusky; Katherine Wesseling-Perry Journal: Nephrol Dial Transplant Date: 2014-01-23 Impact factor: 5.992
Authors: Murat H Sipahioglu; Hamit Kucuk; Aydin Unal; Mehmet G Kaya; Fatih Oguz; Bulent Tokgoz; Oktay Oymak; Cengiz Utas Journal: Perit Dial Int Date: 2011-03-31 Impact factor: 1.756