Influence of oxidative stress on vascular calcification in the setting of coexisting chronic kidney disease and diabetes mellitus

Abstract

Vascular calcification (VC) is a common complication in patients with chronic kidney disease (CKD). Particularly, CKD patients with diabetes mellitus (DM) develop severe VC. Specific mechanisms of VC remain unclear; this study aimed to investigate them in the context of coexisting CKD and DM, mainly regarding oxidative stress. Sprague Dawley rats were randomly divided into six groups as follows: control rats (Control), 5/6 nephrectomized rats (CKD), streptozotocin-injected rats (DM), 5/6 nephrectomized and streptozotocin-injected rats (CKD + DM), CKD + DM rats treated with insulin (CKD + DM + INS), and CKD + DM rats treated with antioxidant apocynin (CKD + DM + APO). At 18 weeks old, the rats were sacrificed for analysis. Compared to the control, DM and CKD groups, calcification of aortas significantly increased in the CKD + DM group. Oxidative stress and osteoblast differentiation-related markers considerably increased in the CKD + DM group compared with the other groups. Moreover, apocynin considerably reduced oxidative stress, osteoblast differentiation-related markers, and aortic calcification despite high blood glucose levels. Our data indicate that coexisting CKD and DM hasten VC primarily through an increase in oxidative stress; anti-oxidative therapy may prevent the VC progression.

Oxidative Stress in Calcific Aortic Valve Stenosis: Protective Role of Natural Antioxidants

“…In addition to VICs, some studies have investigated the calcification inhibitory effect of antioxidants using vascular smooth muscle cells (VSMCs), a rat model of uremic obesity, and adenine-induced chronic renal failure. The antioxidant compounds used in studies were apocynin [ 69 , 70 , 71 ], ellagic acid [ 72 ], gallic acid [ 73 ], puerarin [ 74 , 75 ], silybin [ 76 ], quercetin [ 77 ], diosgenin [ 78 ], vitamin E [ 79 ], 10 dehydrogingerdione (10-DHGD) [ 80 ], and resveratrol [ 81 ].…”

“…Additionally, apocynin downregulated the expression of ERK1/2 phosphorylation in VSMCs, thereby inhibiting osteogenic conversion through ERK1/2 pathway regulation [ 69 ]. In addition to that, apocynin reduced oxidative stress, differentiation-related markers, and aortic calcification despite high blood glucose levels in the chronic kidney disease rat model [ 71 ].…”

Contribution of Oxidative Stress (OS) in Calcific Aortic Valve Disease (CAVD): From Pathophysiology to Therapeutic Targets

“…Fucoxanthin (found in brown seaweed and micro and macro algae) [ 87 , 168 ], Andrographolide extracted from a Chinese medicinal herb (Andrographis paniculata) [ 169 , 170 , 171 ], and Apocynin found in Apocynum cannabinum and Picrorhiza kurroa [ 172 , 173 ] have potent antioxidant properties and attenuated calcification by interfering with the AKT, NF-κB, and ERK1/2 signaling pathways. Additionally, apocynin and celastrol are isolated from the Tripterygium wilfordii Hook F (TWHF) plant, also known as Thunder God Vine lowered NOX expression [ 70 , 174 , 175 ].…”

Bibliometric and Visual Analysis of Vascular Calcification Research

“…Through the potent combination of top keywords and literature, we attribute the research hotspots as follows: 1) The mechanism of VC in CKD or dialysis patients, including inflammation (Yuan et al, 2020), VSMC phenotype of osteogenic differentiation (Yang et al, 2020), overexpression of calcification-promoting factors (oxidative stress) (Watanabe et al, 2020), parathyroid hormone (Imafuku et al, 2020), fibroblast growth factor 23 (Jiang et al, 2020) as well as the suppression of calcification inhibitors (Liu et al, 2018); 2) various pathophysiological changes (atherosclerosis, arterial calcification, arterial stiffness, etc.) accompanied by CVD, and the impact of these changes on the prognosis of patients (Stabley and Towler, 2017;Mszar et al, 2020); 3) comparison of therapeutic effects between open valve replacement surgery and minimally invasive transcatheter valve replacement for aortic valve or heart valve stenosis (Ielasi et al, 2021); and 4) molecular and cellular mechanisms of VC, including various molecular signaling pathways and abnormal proliferation (Miyata et al, 2020) or apoptosis (Boraldi et al, 2021) of cells that regulate VC.…”