Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis

Qu, Kai; Fang, Yan; Xian, Qiming; Zhang, Kun; He, Wen; Dong, Mingqing; Wu, Guicheng

doi:10.3389/fphys.2022.1084604

Cited by 48 publications

(32 citation statements)

References 236 publications

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“…Excessive ROS production can cause damage in mitochondrial DNA and oxidation of important proteins, lipids, and enzymes leading to mitochondrial and cellular dysfunction ( Peng et al, 2019 ). Dysfunctional mitochondria, higher ROS, and reduced NO bioavailability can also signal for release of inflammatory cytokines and chemokines causing activation of inflammatory pathways ( Qu et al, 2022 ; Ciccarelli et al, 2023 ). These are underlying leading factors for many inflammatory and metabolic cardiovascular diseases like atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction

Remex,

Abdullah,

Aishwarya

et al. 2024

Front. Physiol.

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Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1−/−) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1−/−) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1−/− mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1−/− mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1−/− mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

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Section: Discussionmentioning

confidence: 99%

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction

Remex,

Abdullah,

Aishwarya

et al. 2024

Front. Physiol.

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“…Vasoactive substances imbalance in favor of inflammation, vasoconstriction, permeability, oxidative stress and proliferation is associated with endothelial dysfunction, 3 the persistence of which favors atherogenesis, vascular stiffness, platelet aggregation and thrombosis. 4 By means of ultrasonography of the brachial artery, flow-mediated vasodilation (FMV) measures vascular diameter opening in response to sudden blood flow after ischemia. [5][6][7][8] A FMV < 11% showed a sensitivity of 80%, specificity of 86.67%, positive predictive value of 76.66% and negative predictive value of 83.33% for endothelial dysfunction detection.…”

Section: Introductionmentioning

confidence: 99%

Infrared thermography for normal endothelial function screening

Morales-Montalvo,

Cruz-Domínguez,

Martínez-Godínez

et al. 2024

GMM

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Background: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death.Objective: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. Material and methods: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chisquare test, or Fisher's exact test were used. Results: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR-0.22. Conclusion: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.

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“…One of the main mechanisms of atherosclerosis is the formation of advanced glycation end‐products (AGEs), which may lead to loss of collagen elasticity and subsequent increase in arterial stiffness 5 . In addition, excessive mitochondrial reactive oxygen species (ROS) production in the endothelium leads to endothelial dysfunction which may also contribute to the development of arterial stiffness related to diabetes 6,7 . Therefore, providing early interventions in atherosclerosis is vital for diabetic populations.…”

Section: Introductionmentioning

confidence: 99%

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population‐based study

Liang

Zhou

Chen

et al. 2023

Journal of Diabetes

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BackgroundArterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all‐cause mortality.MethodsWe examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid‐femoral (cfPWV) and femoral‐ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic‐femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log‐transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis.ResultsAmong 1079 diabetic patients, biomarkers including high‐density lipoprotein cholesterol, glycated hemoglobin, high‐sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG (R = 0.078, −0.193, −0.155, −0.153, −0.116, and −0.137, respectively) and cfPWV (R = −0.068, 0.175, 0.128, 0.066, 0.202, and 0.062, respectively). Compared with the lowest tertile of afSG, the risk of all‐cause mortality was lower in the highest tertile (hazard ratio 0.543; 95% confidence interval 0.328–0.900).ConclusionCertain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV, suggesting that these putative risk factors are likely to be important atherosclerosis mechanisms in diabetic patients. AfSG may be an independent predictor of mortality among diabetic populations.

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Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis

Cited by 48 publications

References 236 publications

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction

Infrared thermography for normal endothelial function screening

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population‐based study

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