Chronic Hypoxia Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice

Nakano, Daisuke; Hayashi, Toshio; Tazawa, Naoko; Yamashita, Chika; Inamoto, Sakiko; Okuda, Naoki; Mori, Tatsuhiko; Sohmiya, Koichi; Kitaura, Yasushi; Okada, Yoshinori; Matsumura, Yasuo

doi:10.1291/hypres.28.837

Cited by 59 publications

(63 citation statements)

References 41 publications

(30 reference statements)

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“…Oxidative stress initiates several processes involved in atherogenesis, including expression of adhesion molecules, stimulation of VSMC proliferation and migration, apoptosis in the endothelium, oxidation of lipids, activation of matrix metalloproteinases, and altered vasomotor activity (27,28). We confirmed that AT1 deficiency reduced the plasma concentration of 8-isoprostane.…”

Section: Discussionsupporting

confidence: 70%

The Long-Term Effect of Angiotensin II Type 1a Receptor Deficiency on Hypercholesterolemia-Induced Atherosclerosis

Eto¹,

Miyata²,

Shirasawa³

et al. 2008

Hypertens Res

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Section: Discussionsupporting

confidence: 70%

The Long-Term Effect of Angiotensin II Type 1a Receptor Deficiency on Hypercholesterolemia-Induced Atherosclerosis

Eto¹,

Miyata²,

Shirasawa³

et al. 2008

Hypertens Res

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“…Rodent studies have been equivocal. Chronic hypoxia accelerated the development of atherosclerosis in apoE gene-deleted (apoE -/-) mice, along with increased reactive O 2 -production and activated matrix metalloproteinase-9 (MMP-9) in the aorta according to Nakano et al [8]. In any event, chronic hypoxia-related effects should involve hypoxia-inducible factor 1-alpha (HIF-1α).…”

mentioning

confidence: 99%

Hypoxemia as a model for high altitude and cardiovascular risk reduction

Luft

2016

J Mol Med

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Is high-altitude living healthy? Perhaps in wealthy Aspen, Colorado. Data from China suggest that the least healthy place to live there is in Tibet [1]. Of course epidemiological surveys have to be taken with (do I dare say it?) a grain of salt. High altitude could benefit cardiovascular function. Residents of the Himalayan valleys are uniquely adapted to their hypoxic environment in terms of pulmonary vasculature. Bruno et al.[2] inspected their systemic cardiovascular function. They studied 95 high-altitude dwellers and 64 controls. Bruno et al. [2] conducted cardiac ultrasound, flow-mediated dilation (FMD) of the brachial artery, carotid geometry and stiffness, and aortic pulse wave velocity (PWV) in their subjects. Eleven high-altitude dwellers that had reduced FMD were studied after 1 h 100 % O 2 administration. High-altitude dwellers presented lower FMD and hyperemic velocity than controls, while systolic pulmonary artery pressure was higher, despite their adaptation. In multiple regression analysis performed in high-altitude dwellers, hyperemic velocity remained an independent predictor of FMD, after adjustment for baseline brachial artery diameter, room temperature and pulse pressure, explaining almost 10 % of its variance. On the contrary, in controls, brachial artery diameter remained the only independent predictor of FMD, after adjustment for confounders. The 100 % O 2 administration did not modify vascular variables.The risk factors for ischemic heart disease in Tibetan highlanders have been investigated. Fujimoto et al. [3] found that although Tibetans had remarkably high hematocrit values and a decrease of eicosapentaenoic acid in both serum total lipids and serum phospholipid possibly due to their diet, they were considered to have a low incidence of ischemic heart disease. These positive risk factors are likely counteracted by other negative risk factors that were identified. Tibetan highlanders showed a decreased level of palmitic acid and an increased level of linoleic acid in serum phospholipids, which could protect against atherosclerosis. In a study of cardiovascular risk in indigenous Argentinean children living at high altitude, there was a substantially higher prevalence of high triglycerides and low high-density lipoprotein cholesterol, compared to similar children from Buenos Aires [4]. These results are not encouraging. For hypertension, the main cardiovascular risk factor, the epidemiological data at altitude also do not inspire confidence. For instance, Mingji et al. [5] studied the relationship between altitude and the prevalence of hypertension in Tibet. In their investigation, a scatter plot of altitude against overall prevalence revealed a direct correlation. Metaregression analysis revealed a 2 % increase in the prevalence of hypertension with every 100 m increase in altitude. The locations and socioeconomic status of subjects affected the awareness and subsequent treatment and control of hypertension. Thus, an immediate argument that living at high altitude leads to cardiovascu...

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“…It has also been reported that hypoxia accelerates the progression of atherosclerosis (47,62) and modulates vascular remodeling after arterial injury (46). Several studies have provided evidence of hypoxia within the arterial wall in atherosclerosis in an animal model (29) and human disease (63,64).…”

Section: Inflammatory Responses To Arteriosclerosis and Vascular Remomentioning

confidence: 99%

“…ROS generation during hypoxia is reported to be produced from mitochondrial complex II, NADPH oxidase, and xanthine oxidoreductase (42 -45). Therefore, the effects of hypoxia-mediated generation of ROS on atherosclerosis suggest aggravated intimal thickening compared to normoxic exposure of a ballooninjured rabbit (46) and apolipoprotein E-deficient mice (47). Although these studies have shown an effect of low oxygen levels on the initiation and aggravation of vascular remodeling, it remains unclear how decreased oxygen in the pathophysiological microenvironment causes vascular remodeling.…”

Section: Vascular Responses To Hypoxia In Development Of Vascular Remmentioning

confidence: 99%

Pathophysiological Response to Hypoxia — From the Molecular Mechanisms of Malady to Drug Discovery: Inflammatory Responses of Hypoxia-Inducible Factor 1α (HIF-1α) in T Cells Observed in Development of Vascular Remodeling

et al. 2011

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Abstract.Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). Impairment of HIF-1-dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif-1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a Tdependent antigen in the mutant mice. This minireview shows that HIF-1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF-1α.

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Chronic Hypoxia Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice

Cited by 59 publications

References 41 publications

The Long-Term Effect of Angiotensin II Type 1a Receptor Deficiency on Hypercholesterolemia-Induced Atherosclerosis

The Long-Term Effect of Angiotensin II Type 1a Receptor Deficiency on Hypercholesterolemia-Induced Atherosclerosis

Hypoxemia as a model for high altitude and cardiovascular risk reduction

Pathophysiological Response to Hypoxia — From the Molecular Mechanisms of Malady to Drug Discovery: Inflammatory Responses of Hypoxia-Inducible Factor 1α (HIF-1α) in T Cells Observed in Development of Vascular Remodeling

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