• Journal of Ginseng Research
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• 제47권1호
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• pp.144-154
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• 2023

Background: As the major pathophysiological feature of obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) is vital for the occurrence of cardiovascular complications. The activation of calpain-1 mediates the production of endothelial reactive oxygen species (ROS) and impairs nitric oxide (NO) bioavailability, resulting in vascular endothelial dysfunction (VED). Ginsenoside Rg1 is thought to against endothelial cell dysfunction, but the potential mechanism of CIH-induced VED remains unclear. Methods: C57BL/6 mice and human coronary artery endothelial cells (HCAECs) were exposed to CIH following knockout or overexpression of calpain-1. The effect of ginsenoside Rg1 on VED, oxidative stress, mitochondrial dysfunction, and the expression levels of calpain-1, PP2A and p-eNOS were detected both in vivo and in vitro. Results: CIH promoted VED, oxidative stress and mitochondrial dysfunction accompanied by enhanced levels of calpain-1 and PP2A and reduced levels of p-eNOS in mice and cellular levels. Ginsenoside Rg1, calpain-1 knockout, OKA, NAC and TEMPOL treatment protected against CIH-induced VED, oxidative stress and mitochondrial dysfunction, which is likely concomitant with the downregulated protein expression of calpain-1 and PP2A and the upregulation of p-eNOS in mice and cellular levels. Calpain-1 overexpression increased the expression of PP2A, reduced the level of p-eNOS, and accelerated the occurrence and development of VED, oxidative stress and mitochondrial dysfunction in HCAECs exposed to CIH. Moreover, scavengers of O₂^·-, H₂O₂, complex I or mitoKATP abolished CIH-induced impairment in endothelial-dependent relaxation. Conclusion: Ginsenoside Rg1 may alleviate CIH-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.

• Biomolecules & Therapeutics
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• 제24권4호
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• pp.363-370
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• 2016

Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.

• 지질동맥경화학회지
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• 제8권1호
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• pp.1-7
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• 2019

Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.

• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.177-182
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• 2014

This study was to determine the correlation between endothelial function and neuro-endocrine-immune (NEI) network through observing the changes of NEI network under the different endothelial dysfunction models. Three endothelial dysfunction models were established in male Wistar rats after exposure to homocysteine (Hcy), high fat diet (HFD) and Hcy+HFD. The results showed that there was endothelial dysfunction in all three models with varying degrees. However, the expression of NEI network was totally different. Interestingly, treatment with simvastatin was able to improve vascular endothelial function and restored the imbalance of the NEI network, observed in the Hcy+HFD group. The results indicated that NEI network may have a strong association with endothelial function, and this relationship can be used to distinguish different risk factors and evaluate drug effects.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.1-15
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• 2006

Vascular endothelial cell injury or dysfunction has been implicated in the onset and' progression of cardiovascular diseases including atherosclerosis. A number of previous studies have demonstrated that the pro-oxidative and pro-inflammatory pathways within vascular endothelium play an important role in the initiation and progression of atherosclerosis, Recent evidence has provided compelling evidence to indicate that interleukin-4 (IL-4) can induce proc inflammatory environment via oxidative stress-mediated up-regulation of inflammatory mediators such as cytokine, chemokine, and adhesion molecules in vascular endothelial cells. In addition, apoptotic cell death within vascular endothelium has been hypothesized to be involved in the development of atherosclerosis. Emerging evidence has demonstrated that IL-4 can induce apoptosis of human vascular endothelial cells through the caspase-3-dependent pathway, suggesting that IL-4 can increase endothelial cell turnover by accelerated apoptosis, the event which may cause the dysfunction of the vascular endothelium. These studies will have a high probability of revealing new directions that lead to the development of clinical strategies toward the prevention and/or treatment for individuals with inflammatory vascular diseases including atherosclerosis.

• 대한의생명과학회지
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• 제12권3호
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• pp.255-259
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• 2006

Reactive oxygen species (ROS) is one of the main pathological factors in endothelial disorder. For example, an atherosclerosis is induced by the dysfunction of vascular endothelial cells. The dysfunction of vascular endothelial cells cascades to secrete intercellular adhesion molecule (ICAM)-l substance by ROS. Therefore, The ROS is regraded as an important factor of the injury of vascular endothelial cells and inducement of atherosclerosis. Oxygen radical scavengers playa key role to prevention of many diseases mediated by oxidative stress of ROS. In this study, the toxic effect of ROS on vascular endothelial cells and the effect of antioxidant, vitamin E on bovine pulmonary vascular endothelial cell line (BPVEC) treated with hydrogen peroxide were examined by the colorimetric assay. ROS decreased remarkably cell viability according to the dose- and time-dependent manners. In protective effect of vitamin E on BPVEC treated with hydrogen peroxide, vitamin E increased remarkably cell viability compared with control after BPVEC were treated with $15{\mu}M$ hydrogen peroxide for 6 hours. From these results, it is suggested that ROS has cytotoxicity on cultured BPVEC and oxygen radical scavenger such as vitamin E is very effective in prevention of oxidative stress-induced cytotoxicity.

• Journal of Korean Neurosurgical Society
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• 제49권6호
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• pp.373-376
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• 2011

We report a case of a non traumatic spinal subdural hematoma or subarachnoid hematoma manifesting as lumbago, leg pain and bladder dysfunction that showed angiographically occult vascular malformation (AOVM). Although the spinal angiogram did not reveal any vascular abnormality, the follow-up magnetic resonance image showed AOVM. Complete surgical removal was performed due to the aggravated bladder dysfunction. This case highlights the need to consider bleeding due to spinal AOVM, even when angiography is negative.

• Asian Journal of Atmospheric Environment
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• 제1권1호
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• pp.28-35
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• 2007

Accumulated epidemiological and animal studies have suggested that prolonged exposure to ambient particulate matter (PM) is associated with an increased risk of cardiovascular disease and pulmonary dysfunction. While diesel exhaust particles (DEP) contain large variety of compounds, polycyclic aromatic hydrocarbons (PAHs) are a dominant component contaminated in DEP. This article reviews effects of two PAH quinones, 9,10-phenanthraquinone (9,10-PQ) and l,2-naphthoquinone (l,2-NQ), on vascular and respiratory systems.

• 대한한의학방제학회지
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• 제21권1호
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• pp.119-130
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• 2013

Objectives : Diabetes mellitus is the leading cause for vascular complications such as atherosclerosis. The present study is to investigate whether Doinseunggi-tang (DST) improves diabetic vascular dysfunction in type II diabetes. Methods : The db/db mice were treated with high fat/high cholesterol diet and DST (200 mg/kg/day) for 8 weeks. Results : DST significantly lowered blood glucose and systolic blood pressure. In addition, DST also markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol, whereas increased the HDL-cholesterol. Vascular relaxation of aortic rings by acetylcholine or SNP was ameliorated by DST in a dose-dependent manner. Damage of vascular intima and hypertrophic of media was improved by DST. Immunohistological study revealed that DST attenuated the increase of ICAM-1, VCAM-1, and ET-1 expression in thoracic aorta. Conclusions : Taken together, DST suppressed hyperglycemia and diabetic vascular dysfunction in type II db/db mice. The present data suggests that Doinseunggi-tang may be prevent a development of diabetic atherosclerosis.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.201-209
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• 2014

The present study was designed to investigate the efficacy of selective $ET_A$ receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from $5^{th}$ to $8^{th}$ week of L-methionine treatment). On $52^{nd}$ day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective $ET_A$ receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.