Metabolic Profiling in Association with Vascular Endothelial Cell Dysfunction Following Non-Toxic Cadmium Exposure

Abstract

This study aimed to determine the metabolic profile of non-toxic cadmium (Cd)-induced dysfunctional endothelial cells using human umbilical vein endothelial cells (HUVECs). HUVECs (n = 6 per group) were treated with 0, 1, 5, or 10 μM cadmium chloride (CdCl2) for 48 h. Cell phenotypes, including nitric oxide (NO) production, the inflammatory response, and oxidative stress, were evaluated in Cd-exposed and control HUVECs. Cd-exposed and control HUVECs were analysed using gas chromatography time-of-flight/mass spectrometry. Compared to control HUVECs, Cd-exposed HUVECs were dysfunctional, exhibiting decreased NO production, a proinflammatory state, and non-significant oxidative stress. Further metabolic profiling revealed 24 significantly-altered metabolites in the dysfunctional endothelial cells. The significantly-altered metabolites were involved in the impaired tricarboxylic acid (TCA) cycle, activated pyruvate metabolism, up-regulated glucogenic amino acid metabolism, and increased pyrimidine metabolism. The current metabolic findings further suggest that the metabolic changes linked to TCA cycle dysfunction, glycosylation of the hexosamine biosynthesis pathway (HBP), and compensatory responses to genomic instability and energy deficiency may be generally associated with dysfunctional phenotypes, characterized by decreased NO production, a proinflammatory state, and non-significant oxidative stress, in endothelial cells following non-toxic Cd exposure.

Limb Preservation Using Edetate Disodium-based Chelation in Patients with Diabetes and Critical Limb Ischemia: An Open-label Pilot Study

“…Unfortunately, the design and small sample size of this pilot study lacked statistical power to draw definite conclusions on the effect of chelation therapy on vascular flow. Toxic metals may lead to endothelial dysfunction by decreasing nitric oxide production and increasing oxidative stress, leading to vasoconstriction and increased basal tone in the microcirculation [30]. An alternate hypothesis not involving toxic metals is that the infusions simply decalcify advanced atherosclerotic lesions.…”

“…Skin perfusion pressures (mmHg) in the target vascular bed of the affected foot demonstrate a trend towards improvement after edetate disodium infusions (median (IQR): 22 , 46 (18-69) and 36 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) at baseline, 20 and 40 infusions, respectively, P=0.06). The median perfusion pressures in the contralateral foot did not significantly change during follow-up ( Table 6).…”

Cadmium exposure induces endothelial dysfunction via disturbing lipid metabolism in human microvascular endothelial cells

“…And as a potent endogenous vasoconstrictor, ET‐1 acts via two receptors, ETA and ETB (Gopalakrishna, Pennington, Karaa, & Clemens, 2016; Hans, Deseure, & Adriaensen, 2008; Wang et al, 2017; Wang et al, 2018). Cd reduces NO levels and inhibits eNOS expression (Majumder et al, 2008; Yoopan, Watcharasit, Wongsawatkul, Piyachaturawat, & Satayavivad, 2008; Zhong, Li, Nong, Mao, & Pan, 2017). While endothelial injury is an important process that contributes to the development of Cd‐induced hypertension, lower concentration of cadmium is not enough to kill endothelial cells.…”

Metabolomic Profiling of Patients With Cardiovascular Diseases

“…определяли метаболомный профиль нетоксичной кадмий-индуцированной дисфункции эндотелия с использованием клеток пупочной вены человека. В ходе нецелевого метаболомного исследования идентифицировано 24 эндогенных метаболита и 7 метаболических путей (1 -глицин, серин и треонин; 2 -цикл трикарбоновых кислот; 3 -аргинин и пролин; 4 -аланин, аспартат и глутамат; 5 -цистеин и метионин; 6 -пиримидин; 7 -пируват), которые были значительно изменены в исследуемой культуре по сравнению с контрольной группой [17]. Это исследование позволяет предполо-жить, что метаболомное профилирование может быть применено для определения биомаркеров дисфункции эндотелия в клинической практике.…”