Shedding of TNF-α receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus

Fernández‐Real, José Manuel; Laínez, Begoña; Vendrell, Joan; Rigla, Mercedes; Castro, Antoni; Peñarroja, Georgina; Broch, Montserrat; Pérez, Antonio; Richart, C; Engel, Pablo; Ricart, Wifredo

doi:10.1152/ajpendo.00444.2001

Cited by 68 publications

(47 citation statements)

References 35 publications

(36 reference statements)

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“…7 TNF-a appears to be the critical cytokine in the process of endothelial stunning, 37 and has been associated to the insulin-resistant syndrome 16,40 and to HBP. 34,45 However, prospective cohort studies are needed to elucidate whether cytokine elevation predicts the development or is just a consequence of HBP. Knowledge of the contribution of CMI to HBP development could facilitate current efforts on detection, evaluation, and treatment of hypertension.…”

Section: Resultsmentioning

confidence: 99%

“…27,29 However, these studies have failed to control for other risk factors for HBP. On the other hand, Fernández-Real et al 45 have shown that the ratio of soluble TNF-a receptor 1 and soluble TNF-a receptor 2 (sTNFR1/ sTNFR2), a correlate of the degree of activation of the TNF-a system, is positively and significantly associated with systolic and diastolic blood pressure, and that lowering blood pressure decreases the sTNFR1/sTNFR2 ratio. Prolonged periods of low-grade systemic inflammation may explain the higher risk of HBP observed among subjects with obesity.…”

Section: Epidemiologic Evidencementioning

confidence: 99%

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Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence

2003

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Section: Resultsmentioning

confidence: 99%

Section: Epidemiologic Evidencementioning

confidence: 99%

Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence

2003

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“…However, in experimental studies the degree of activation of the TNF-a system has been positively and significantly associated with systolic and diastolic BP. 33 Besides, TNF-a decreases endothelial nitric oxide synthase mRNA level by shortening its half-life. 34 This may result in decreased bioavailability of nitric oxide and lead to endothelial dysfunction, chronic vasoconstriction, and elevated BP.…”

Section: Discussionmentioning

confidence: 99%

Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension

et al. 2004

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High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-a), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-a, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP X140 and/or diastolic BP X90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P ¼ 0.003), third (PR: 2.32; P ¼ 0.031), and fourth quartiles (PR: 2.30; P ¼ 0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-a levels were 1.41 (P ¼ 0.014) for the second; 1.59 (P ¼ 0.001) for the third; and 1.61 (P ¼ 0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-a and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.

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“…Both genes encode peptides that can be produced by adipose tissue, and that can influence adipogenesis and lipogenesis in an autocrine/paracrine manner; in addition, when released into the circulation, they may regulate BP. 25,[27][28][29] As such, either of the 2 genes may exert pleiotropic effects on adiposity and BP. Alternatively, the locus may include 2 closely linked genes that cosegregate within families, with one being involved in the regulation of adiposity and the other in the control of BP.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

et al. 2005

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Abstract-Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having Ն2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (Ն70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density Ͻ10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] scoreϭ2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD scoreϭ3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD scoreϭ3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder. Key Words: hypertension, obesity Ⅲ genetics E ssential hypertension is a heterogeneous disorder that develops because of several overlapping subsets of pathophysiological mechanisms. Obesity is a leading risk factor for the disorder, and as such, may be a key element in one of these subsets. Prospective cohort investigations have demonstrated positive correlations between weight gain and blood pressure (BP) elevation. 1 For example, in the Framingham Study, it was estimated that for each 4.5 kg of weight gain, there is an associated increase in systolic BP of 4 mm Hg in both men and women. 2 Pathophysiological mechanisms linking the increases in adiposity to the elevations in BP are not very well understood. They may include alterations in renal handling of sodium and water, sympathetic nervous system activity, insulin sensitivity, and fatty acid metabolism, 3 with some of these alterations being induced by hormones, growth factors, and cytokines expressed by adipose tissue in response to its expansion.Hypertension and obesity are multifactorial traits determined by a complex interplay of genes and environments. 4 A number of genes contribute to the determination of each of these traits, and their actions are simple, additive, or more complex, characterized by phenomena such as epistasis and pleiotropy. Furthermore, hypertension and ...

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Shedding of TNF-α receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus

Cited by 68 publications

References 35 publications

Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence

Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence

Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

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