The role of chemokines in human cardiovascular pathology: enhanced biological insights

Shin, William S.; Szuba, Andrzej; Rockson, Stanley G.

doi:10.1016/s0021-9150(01)00571-8

Cited by 169 publications

(111 citation statements)

References 94 publications

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“…These new findings are of interest since chemokines such as IL-8 and MCP-1 have been suggested to be involved in the pathogenesis of diseases associated with excess amounts of adipose tissue e.g. atherosclerosis and cardiovascular disease (25,35). In addition, circulating levels of IL-8 have been reported to be increased in patients with type 1 and type 2 diabetes (26) linking these chemokines with insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men

Bruun

Verdich²,

Toubro³

et al. 2003

European Journal of Endocrinology

265

162

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Objective: To study the association between anthropometric and metabolic parameters as well as the effect of weight loss on plasma levels of the adipose tissue-derived cytokines interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in abdominal obese men. Subjects: Nineteen obese (mean body mass index (BMI): 38:6^0:6 kg=m 2 ) and ten lean men (mean BMI: 23:4^0:4 kg=m 2 ) were included in the study. The obese subjects received a 4.2 MJ/day diet for 8 weeks, followed by 8 weeks on energy restriction (6.2 MJ/day) and 8 weeks on a weight-maintenance diet. Measurements: A dual energy X-ray absorptiometry (DEXA)-scan was performed to estimate body composition. Plasma levels of IL-8, IL-6 and TNF-a were measured by a specific ELISA method. Insulin sensitivity was assessed by the homeostasis model assessment method (HOMA). Results: Plasma levels of IL-8 and IL-6 were 30-40% higher in obese as compared with lean subjects ðP , 0:05Þ; whereas no group difference in TNF-a was observed. During the intervention, obese subjects obtained a 30% reduction in fat mass ðP , 0:001Þ; fasting insulin ðP , 0:05Þ and HOMA ðP , 0:05Þ: Plasma levels of TNF-a and IL-6 were decreased by 25-30% ðP , 0:001Þ but IL-8 was increased by 30% ðP , 0:001Þ after weight loss. IL-8 and IL-6 were correlated with measures of insulin resistance, and changes in IL-6 but not IL-8 were correlated with the improvement in insulin sensitivity after weight loss. Conclusion: Plasma levels of IL-8 and IL-6 were found to be increased and were correlated with measures of insulin resistance in abdominal obese male subjects. Weight loss was associated with changes in the circulating levels of IL-8, IL-6 and TNF-a indicating that these cytokines are influenced by weight loss.

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Section: Discussionmentioning

confidence: 99%

Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men

Bruun

Verdich²,

Toubro³

et al. 2003

European Journal of Endocrinology

265

162

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“…It recruits neutrophilic granulocytes, accelerates vascular growth, and induces smooth muscle cells to proliferate and migrate [5] . IL-8 is an important immunological inflammatory regulatory factor.…”

Section: Discussionmentioning

confidence: 99%

Expression change of interleukin-8 gene in rabbit basilar artery after subarachnoid hemorrhage

et al. 2007

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Objective To study the expression change of interleukin-8 (IL-8) gene in the basilar artery of rabbit and the effect of IL-8 on the development of cerebral vasospasm induced by experimental subarachnoid hemorrhage (SAH). Methods Thirty five healthy Japanese White Rabbits were randomly divided into saline-control group and experimental group. The experimental group was subdivided into four groups, representing day 1, 4, 7 and 14 after the first blood injection of SAH. The delayed cerebral vasospasm (DCVS) model was established by double injection of autologous blood into the cisterna magna. The expression change of cytokine IL-8 mRNA in the basilar artery was analyzed by RT-PCR. Results The expression of IL-8 gene increased on day 4-7 after the first blood injection of SAH compared with control (P < 0.001), and decreased to normal on day 14. The expression of IL-8 gene in the SAH groups were positively correlated with the degree of basilar artery stenosis (r = 0.642, P < 0.01). Conclusion The expression level of IL-8 gene in basilar arteries was intimately associated with the degree of cerebral vasospasm, suggesting that IL-8 may play an important role in the DCVS after SAH as an immunological inflammatory factor.

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“…Importantly, CCL2 is reported to be play a role in most of the processes involved in the formation of atherosclerotic lesions [24] and is strongly expressed in human atheromatous lesions but not in normal arteries [25]. Furthermore, the selective knockout of CCR2, the receptor for CCL2, prevents the initiation of the atherosclerotic process in vivo [26].…”

Section: Discussionmentioning

confidence: 99%

Increased expression of CCAAT/enhancer binding protein-β and -δ and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats

et al. 2006

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Aims/hypothesis We evaluated whether hyperinsulinaemia stimulates the expression of transcription factor CCAAT/ enhancer binding protein (C/EBP)-β and C/EBP-δ and leads to the induction of the chemokine (C-C motif) ligand 2 gene (Ccl2, also known as MCP-1) expression in aortas. Methods Hyperinsulinaemia was induced by feeding rats a high-fructose diet. CCL2 production was analysed by ELISA. The expression of Ccl2, Cebpb and Cebpd mRNAs was investigated by quantitative RT-PCR. The binding of C/EBP-β to Ccl2 was assessed by chromatin immunoprecipitation (ChIP) assay. Results Insulin at a concentration of 10 nmol/l significantly stimulated the expression of Cebpb,Cebpd and Ccl2 mRNAs, depending on activation of phosphatidylinositol 3-kinase (PI3K) in cultured vascular smooth muscle cells. The knockdown of C/EBP-β with siRNA abolished the insulin-induced Ccl2 mRNA expression. In the aortas from fructose-fed rats, the levels of phosphorylation of Akt/protein kinase B, a downstream effector of PI3K, were also increased. The expression of Cebpb, Cebpd and Ccl2 mRNAs in the aortas from fructose-fed rats were significantly elevated, by 330, 300 and 300%, respectively, compared with those of controlfed rats. The induction Ccl2 mRNA expression in the aortas was significantly correlated with the expression of Cebpb and Cebpd mRNAs in the aortas. Furthermore, the ChIP assay showed elevated binding of C/EBP-β to the 5′ upstream region of Ccl2 in the aortas from fructose-fed rats. Conclusions/interpretation These findings clearly indicate the role of C/EBPs in the mechanism of upregulation of CCL2, an inflammation-related protein, observed in the hyperinsulinaemic state, which may initiate the process of atherosclerosis.

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The role of chemokines in human cardiovascular pathology: enhanced biological insights

Cited by 169 publications

References 94 publications

Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men

Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men

Expression change of interleukin-8 gene in rabbit basilar artery after subarachnoid hemorrhage

Increased expression of CCAAT/enhancer binding protein-β and -δ and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats

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