title: p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells.
abstract: Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients. p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE(-/-) mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n = 20) and PCS-treated group (n = 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 μmol/L PCS for in vitro evaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Yanjia
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Run
authors.initials: R
authors.lastname: Du
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. rjzhangruiyan@aliyun.com.|Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. rjzhangruiyan@aliyun.com.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. jinwei1125@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003408:Cresols / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009392:Nephrectomy; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D013463:Sulfuric Acid Esters / Q000009:adverse effects*
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate
keywords: atherosclerosis; p-cresyl sulfate; plaque stability; vascular smooth muscle cell