p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells.
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.
['Han|Hui|H|', 'Chen|Yanjia|Y|', 'Zhu|Zhengbin|Z|', 'Su|Xiuxiu|X|', 'Ni|Jingwei|J|', 'Du|Run|R|', 'Zhang|Ruiyan|R|', 'Jin|Wei|W|']
D000818:Animals D001011:Aorta D017209:Apoptosis D002465:Cell Movement D049109:Cell Proliferation D002478:Cells, Cultured D003408:Cresols D059305:Diet, High-Fat D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D009392:Nephrectomy D058226:Plaque, Atherosclerotic D011897:Random Allocation D051381:Rats D013463:Sulfuric Acid Esters
p-cresyl sulfate vascular smooth muscle cell atherosclerosis plaque stability