Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke

Borné, Yan; Fagerberg, Björn; Persson, Margaretha; Östling, Gerd; Söderholm, Martin; Hedblad, Bo; Sällsten, Gerd; Barregård, Lars; Engström, Gunnar

doi:10.1161/jaha.117.006415

Cited by 55 publications

(36 citation statements)

References 30 publications

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“…The health effects of cadmium exposure have been reported as increased risks of CVD, atherosclerosis [ 45 ], stroke [ 46 , 47 ], high blood pressure, hypertension [ 32 , 48 ], and cancer [ 21 ]. Among these diseases, the results of several experimental studies support the effect of cadmium toxicity on CVD risk, including endothelial cell death, oxidative stress, smooth muscle cell accumulation, and vascular inflammation [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Blood Cadmium with Cardiovascular Disease in Korea: From the Korea National Health and Nutrition Examination Survey 2008–2013 and 2016

Jeong

Yun

Kim

et al. 2020

IJERPH

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Cardiovascular disease (CVD) is the leading cause of death globally, although the mortality rate has declined with improved technology and risk factor control. The incidence rate of stroke, one of the CVDs, is increasing in young adults, whereas it is decreasing in the elderly. The risk factors for CVD may differ between young adults and the elderly. Previous studies have suggested that cadmium was a potential CVD risk factor in the overall and middle-aged to elderly populations. We assessed the associations between cadmium and CVD events in the Korean population aged 20–59 years using the 2008–2013 and 2016 Korea National Health and Nutrition Examination Survey (KNHANES), a population-based cross-sectional study. Among 10,626 participants aged 20–59 years, those with high blood cadmium (BCd) level (>1.874 µg/L, 90th percentile) were higher associated with stroke and hypertension (stroke: odds ratio (OR), 2.39; 95% confidence interval (CI), 1.03–5.56; hypertension: OR, 1.46; 95% CI, 1.20–1.76). The strongest association between high blood cadmium concentrations and hypertension was among current smokers. Ischemic heart disease (IHD) was not associated with high blood cadmium level. These findings suggest that high blood cadmium levels may be associated with prevalent stroke and hypertension in the Korean population under 60 years of age.

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Section: Discussionmentioning

confidence: 99%

Association of Blood Cadmium with Cardiovascular Disease in Korea: From the Korea National Health and Nutrition Examination Survey 2008–2013 and 2016

Jeong

Yun

Kim

et al. 2020

IJERPH

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“…Carotid artery stenosis is closely related to ischemic stroke (Eckstein et al, 2013;Gupta et al, 2012;Lu & Wang, 2016) and is mainly caused by carotid atherosclerosis (Adams, Bojara, & Schunk, 2018;Liu et al, 2017) because of embolic sequelae as a consequence of underlying atherosclerosis which can incur/ cause secondary hemodynamic disturbances. The role of inflammation in the pathogenesis of carotid atherosclerosis has been well established (Borne et al, 2017;Casiglia & Tikhonoff, 2007), and the role of various inflammatory cells and mediators involved in carotid disease and stroke should be well investigated in order to better predict/ identify at-risk patients (Ammirati, Moroni, Norata, Magnoni, & Camici, 2015;Casiglia & Tikhonoff, 2007;Horne et al, 2005;Woollard & Geissmann, 2010).…”

Section: Introductionmentioning

confidence: 99%

Monocyte/lymphocyte ratio is associated with carotid stenosis in ischemic stroke: A retrospective analysis

et al. 2019

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Background Carotid artery stenosis, mainly caused by carotid atherosclerosis, is related to ischemic stroke. This study was to investigate whether monocyte/lymphocyte ratio (MLR) was associated with increased severity of carotid stenosis in patients with ischemic stroke. Methods A total of 395 participants with ischemic stroke were retrospectively analyzed. The severity of carotid stenosis was evaluated by ultrasound examination. Patients were divided into two groups: nonsevere stenosis group and severe stenosis group. Multivariate logistic analysis was used to evaluate risk factors. Results A significant correlation was found between MLR and the severity of carotid stenosis in patients with ischemic stroke. MLR was the independent risk factor of carotid stenosis (OR: 9.74, 95% CI: 1.16–81.54). In the ROC curves analysis, a cutoff value of 0.20 for MLR predicted the severity of carotid stenosis with a sensitivity of 80.40% and specificity of 26.40% (ROC area under the curve: 0.598, 95% CI: 0.53–0.67, p = .004). Conclusion Monocyte/lymphocyte ratio plays important roles in carotid stenosis in patients with ischemic stroke and is an independent risk factor of the severity of carotid stenosis. Therefore, MLR might be considered a potential index in the diagnosis of carotid stenosis in patients with ischemic stroke.

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“…Cigarette smoke is one of major source of Cd exposure. In epidemiologic studies, it has been shown that environmental cadmium exposure was associated with increased risk of stroke [7, 34]. Cd induces phosphorylation of CREB [35], which is also observed in the blood of smokers [36].…”

Section: Discussionmentioning

confidence: 99%

“…Cd is also one of major components of air particulate matters that associated with acute changes in cardiovascular or respiratory physiology [5]. A few studies report a significant correlation between the increased risk for stroke and Cd or cigarette smoke extract (CSE) exposure [6, 7]. Brain ischemia triggers an inflammatory reaction that contributes to the progression of brain diseases [8].…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke extracts and cadmium induce COX-2 expression through γ-secretase-mediated p38 MAPK activation in C6 astroglia cells

Lim

Park

et al. 2019

PLoS ONE

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Exposure to cigarette smoke has been implicated in the progression of cerebrovascular and neurological disorders like stroke through inflammation and blood-brain barrier disruption. In this study, we investigated the signaling cascade activated by cigarette smoke extracts (CSE) and cadmium (Cd) resulting in the COX-2 induction in C6 rat astroglia cells. CSE or Cd induced Notch1 cleavage and activated p38 MAPK and CREB signaling pathways in C6 astroglia cells. Knockdown of nicastrin using siRNA or γ-secretase inhibitors, DAPT and L-685,486, reduced Notch1 cleavage and phosphorylation of p38 MAPK and CREB, while phosphorylation of ERK and JNK remained unaffected. Additionally, the blockage of γ-secretase activity did not show any effect on the phosphorylation of AKT, another upstream activator of CREB, indicating that γ-secretase-mediated CREB activation occurs via p38 MAPK. γ-secretase inhibitor also inhibited the CSE and Cd-mediated increase in the expression of COX-2. Furthermore, recombinant overexpression of Notch1 intracellular domain resulted in an increase in the expression of COX-2. Notch signaling induced by CSE and Cd induced apoptosis in C6 cells. Our results demonstrate that CSE exposure activated the p38 MAPK and CREB-mediated induction in COX-2 expression in astrocytes via γ-secretase-mediated Notch1 signaling. Our data provides novel insights into the potential mechanism of pro-inflammatory response activated by exposure to cigarette smoke.

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Cadmium, Carotid Atherosclerosis, and Incidence of Ischemic Stroke

Cited by 55 publications

References 30 publications

Association of Blood Cadmium with Cardiovascular Disease in Korea: From the Korea National Health and Nutrition Examination Survey 2008–2013 and 2016

Association of Blood Cadmium with Cardiovascular Disease in Korea: From the Korea National Health and Nutrition Examination Survey 2008–2013 and 2016

Monocyte/lymphocyte ratio is associated with carotid stenosis in ischemic stroke: A retrospective analysis

Cigarette smoke extracts and cadmium induce COX-2 expression through γ-secretase-mediated p38 MAPK activation in C6 astroglia cells

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