Pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin

Chen, Yang Xin; Wang, Xiaoqiao; Fu, Yao‐Shi; Yao, You Jie; Kong, Min Yi; Nie, Ru Qiong; Wang, Jing Feng

doi:10.1016/j.ijcard.2009.06.019

Cited by 20 publications

(16 citation statements)

References 32 publications

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“…The enhanced response to EFS was normalized by treatment with rosuvastatin. To our knowledge, this is the first study to show this novel effect The decrease in non-HDL cholesterol levels could be attributed to the observed effects of the statin, although other well-known described effects of statins, such as antioxidant and anti-inflammatory effects, might have contributed to the vascular effects of rosuvastatin (Devaraj et al, 2006;Cachofeiro et al, 2008;Chen et al, 2009).…”

Section: Discussionmentioning

confidence: 66%

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Blanco-Rivero

Heras

Martín-Fernández

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSEWe investigated whether high-fat diet (HFD)-induced obesity was associated with changed function of components of the mesenteric innervation (adrenergic, sensory and nitrergic), the mechanisms involved and the possible effects of rosuvastatin on these changes. EXPERIMENTAL APPROACHMale Wistar rats were divided into three groups. (i) rats fed a standard diet (control group); (ii) rats fed a HFD (33.5% fat) for 7 weeks; and (iii) rats fed a HFD and treated with rosuvastatin (15 mg·kg) for 7 weeks. Segments of isolated mesenteric arteries were exposed to electric field stimulation (EFS) with or without tetrodotoxin, phentolamine, 7-nitroindazole (7NI) or N w nitro-L-arginine methyl ester (L-NAME). Noradrenaline, ATP and NO release, and nNOS expression were also measured. KEY RESULTSEFS induced a greater frequency-dependent contraction in obese than in control rats. In HFD rats, phentolamine reduced contractions elicited by EFS, but noradrenaline release was greater and ATP release decreased. L-NAME and 7NI increased contractions to EFS in segments from control rats, but not in those from HFD rats. NO release and nNOS expression were lower in arterial segments from HFD rats than in control rats. All these changes in HFD rats were reversed by treatment with rosuvastatin. CONCLUSIONS AND IMPLICATIONSNeural control of mesenteric vasomotor tone was altered in HFD rats. Enhanced adrenergic and diminished nitrergic components both contributed to increased vasoconstrictor responses to EFS. All these changes were reversed by rosuvastatin, indicating novel mechanisms of statins in neural regulation of vascular tone.

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Section: Discussionmentioning

confidence: 66%

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Blanco-Rivero

Heras

Martín-Fernández

et al. 2010

British J Pharmacology

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“…Rabbits fed an HFD have an increase in blood lipid levels as well as inflammatory markers such as IL-6 (9). These rabbits also display increased ET-1 and endothelial dysfunction (9). Therefore, high fat is capable of inducing inflammation, leading to endothelial dysfunction in association with elevated vascular ET-1.…”

Section: Discussionmentioning

confidence: 96%

Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium

Simeone

Li²,

Paradis³

et al. 2011

Physiological Genomics

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Simeone SM, Li MW, Paradis P, Schiffrin EL. Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium. Physiol Genomics 43: 148 -160, 2011. First published November 2, 2010; doi:10.1152/physiolgenomics.00218.2009.-Endothelin (ET)-1 plays an important pathophysiological role in several vascular diseases including hypertension and atherosclerosis. Transgenic mice overexpressing human preproET-1 selectively in the endothelium (eET-1) exhibit vascular injury in the absence of blood pressure elevation. ET-1 overexpression may induce vascular injury by inducing changes in gene expression. To understand mechanisms whereby ET-1 induces vascular damage, vascular gene expression profiling was performed using DNA microarrays. RNA from mesenteric arteries of male and female young (6 -7 wk) and mature (6 -8 mo) eET-1 and wild-type (WT) mice was isolated, and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray and FlexArray software. Data were analyzed using a relaxed and a stringent statistical approach. The gene lists were compared and analyzed as well with Ingenuity Pathway Analysis. The most common change was an increase in the expression of lipid metabolism genes. Four of these genes were validated by qPCR, cyp51, dgat2, and scd1 genes in young and elovl6 in both young and mature male mice, supporting a role of ET-1 in atherosclerosis. To test the hypothesis that ET-1 participates in mechanisms leading to atherosclerosis, we crossed eET-1 with atherosclerosisprone apoE Ϫ/Ϫ mice to determine whether ET-1 overexpression exacerbates high-fat diet (HFD)-induced atherosclerosis using oil red O staining of descending thoracic aorta. HFD increased lipid plaques by 3-, 27-, and 86-fold in eET-1, apoE Ϫ/Ϫ , and crossed mice, respectively, vs. WT. This suggests that increased endothelial ET-1 expression results in early changes in gene expression in the vascular wall that enhance lipid biosynthesis and accelerate progression of atherosclerosis. aorta; artery; lipid biosynthesis; vascular remodeling; inflammation; atherosclerosis ESSENTIAL HYPERTENSION IS characterized by increased peripheral resistance to blood flow (48). The vasoconstrictor peptide endothelin-1 (ET-1) (58), which has a critical role in normal development and probably in regulation of blood flow in normal physiology (24), has been associated with increased blood pressure (BP) in human and experimental animal studies (1, 47). ET-1 has also been implicated in other pathophysiological conditions such as pulmonary hypertension (16), atherosclerosis (4, 22, 56), heart failure (17,19,35,46,52), myocardial infarction (8, 34), and chronic renal failure (1, 11, 37), among others (49). ET-1 is produced predominantly by endothelial cells but also by many other cells and tissues such as vascular smooth muscle cells, fibroblasts, macrophages/ monocytes and cardiomyocytes, as well as noncardiovascular cells and tissues such as renal tubular epithelial cells, glial cells, and pituitary cell...

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“…"However, the underlying mechanisms for the phenomena mentioned above are still unclear" authors described in their article. Subsequently, authors scientifically indicated it that "We hypothesize that inflammatory response may play pivotal role for all the phenomena" [1]. Besides the very similar presentation to our previous published paper in this paragraph, academically, there may be of an obvious trend that authors take up the concept from previous' papers including our studies due to no any quotations with regard to the hypotheses and presentation [3].…”

Section: Dear Editormentioning

confidence: 51%

“…We read with interest the paper entitled as "pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin" by authors Chen YX et al, which was published in International Journal of Cardiology 2011;146: 140-144 [1]. Besides, authors should be congratulated for their article that is through and clear.…”

Section: Dear Editormentioning

confidence: 99%

“…Firstly, authors point out in the section of introduction that withdrawal of statin would result in a rapid de-protection for cardiovascular disease presenting as increased stroke, death as well as nonfatal myocardial infarction or increased risk of other early clinical complications, platelet hyperactivity as well as vascular endothelial dysfunction [1]. "However, the underlying mechanisms for the phenomena mentioned above are still unclear" authors described in their article.…”

Section: Dear Editormentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory rebound phenomenon after abrupt withdrawal of statin is a mature point of view but not hypotheses

2011

International Journal of Cardiology

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Pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin

Cited by 20 publications

References 32 publications

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats

Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium

Inflammatory rebound phenomenon after abrupt withdrawal of statin is a mature point of view but not hypotheses

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