Pro‐inflammatory cytokines in patients with essential hypertension

Peeters, A. C. T. M.; Netea, M.G.; Janssen, Manoe J.; Kullberg, Bart Jan; Meer, J.W.M. van der; Thien, Th.

doi:10.1046/j.1365-2362.2001.00743.x

Cited by 128 publications

(98 citation statements)

References 30 publications

(48 reference statements)

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“…Similar disagreements was also observed in studies of human hypertensives, which showed increased circulating levels of IL-1β in one study and decreased levels in another (Dalekos et al, 1997;Dalekos et al, 1996;Peeters et al, 2001). It has been suggested that genetic differences in study populations may account for the variability where these differences are the cause of differences in cytokine expression and are wholly a characteristic of hypertension.…”

Section: Discussionsupporting

confidence: 60%

Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat

Peltsch

Khurana

Byrne

et al. 2016

Can. J. Physiol. Pharmacol.

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https://mc06.manuscriptcentral.com/cjpp-pubs ABSTRACTPhenylethanolamine N-methyltransferase (PNMT) is the terminal enzyme in the catecholamine biosynthetic pathway responsible for adrenaline biosynthesis. Adrenaline is involved in the sympathetic control of blood pressure; it augments cardiac function by increasing stroke volume and cardiac output. Genetic mapping studies have linked the PNMT gene to hypertension. This study examined the expression of cardiac PNMT and changes in its transcriptional regulators in the spontaneously hypertensive (SHR) and wild type Wistar-Kyoto (WKY) rats. SHR exhibit elevated levels of corticosterone, and lower levels of the cytokine IL-1 β, revealing systemic differences between SHR and WKY. PNMT mRNA was significantly increased in all chambers of the heart in the SHR, with the greatest increase in the right atrium. Transcriptional regulators of the PNMT promoter show elevated expression of Egr-1, Sp1, AP-2 and GR mRNA in all chambers of the SHR heart, while protein levels of Sp1, Egr-1 and GR were elevated only in the RA. Interestingly, only AP-2 protein-DNA binding was increased, suggesting it may be a key regulator of cardiac PNMT in SHR. This study provides the first insights into the molecular mechanisms involved in the dysregulation of cardiac PNMT in a genetic model of hypertension.

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Section: Discussionsupporting

confidence: 60%

Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat

Peltsch

Khurana

Byrne

et al. 2016

Can. J. Physiol. Pharmacol.

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“…48 Similar observations have been made in hypertensive patients. 49 Our important new finding was that treatment with PNU-282987 did not reduce blood pressure but decreased the levels of these inflammatory factors in SHR tissues in most cases and greatly attenuated EOD as assessed by both light and electron microscopy. Thus, pharmacological rescue of the deficit in ␣7nAChR signaling in SHRs has anti-inflammatory effects.…”

Section: Et Al ␣7nachr and Hypertensive Organ Damage 303mentioning

confidence: 83%

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

et al. 2011

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Abstract-Inflammatory responses are associated with the genesis and progression of end-organ damage (EOD) in hypertension. A role for the ␣7 nicotinic acetylcholine receptor (␣7nAChR) in inflammation has recently been identified. We tested the hypothesis that ␣7nAChR dysfunction contributes to hypertensive EOD. In both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta coarctation-induced hypertension, atropine-induced tachycardia was blunted compared with normotensive controls. Both models of hypertension were associated with deficits in expression of the vesicular acetylcholine transporter and the ␣7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta coarctation, deficits in aortic vesicular acetylcholine transporter and ␣7nAChR were present both above and below the coarctation site, indicating that they were independent of the level of arterial pressure itself. Hypertension in 40-week-old SHRs was associated with cardiac and aortic hypertrophy. Morphological abnormalities consistent with EOD, along with elevated tissue levels of proinflammatory cytokines (tumor necrosis factor-␣, interleukin-1␤, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic treatment of SHRs with the ␣7nAChR agonist PNU-282987 relieved EOD and inhibited tissue levels of proinflammatory cytokines and activation of nuclear factor B. Greater serum levels of proinflammatory cytokines and more severe damage in the heart, aorta, and kidney were seen in ␣7nAChR Ϫ/Ϫ mice subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis of EOD in models of hypertension of varying etiology. This pathway may provide a new target for preventing cardiovascular disease resulting from hypertension. (Hypertension. 2011;57:298-307.) • Online Data Supplement Key Words: acetylcholine Ⅲ ␣7 nicotinic acetylcholine receptor Ⅲ inflammation Ⅲ hypertension Ⅲ end-organ damage H ypertension is a major risk factor for myocardial infarction, heart failure, stroke, and kidney dysfunction. Endorgan damage (EOD), including cardiac hypertrophy and myocyte dysfunction, vascular remodeling, and renal lesions, is a crucial mediatory link between hypertension and the development of these cardiovascular events. 1 Therefore, a better understanding of the mechanisms leading to hypertensive EOD could provide new avenues for prevention of cardiovascular events. Inflammation is very important in the genesis and development of EOD. 2,3 Furthermore, the reninangiotensin system can contribute to EOD, at least partly by promoting inflammation. 4 -7 However, cardiovascular inflammation and EOD can also occur without renin-angiotensin system activation, 8 so other mechanisms must also operate.Recent evidence indicates that neuronal 9 -11 cholinergic systems influence inflammatory responses by controlling the release of tumor necrosis factor (TNF)-␣, interleukin-(⌱L)-1␤, and IL-6 and that nonneuronal acetylcholine synthesis and rele...

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“…Since the interaction in the risk for EH of one allele of the HLA system (a key element of the immune response) and an infectious agent (C. pneumoniae) has been described in our study, the probability that immune and inflammatory mechanisms are important factors in the pathogenesis of EH (as has been well documented in atherosclerosis at the cellular 21 and biochemical level 22 ) is clearly higher than that previously suspected. On the basis of several experimental findings, [23][24][25][26][27][28] it has been hypothesized that chronic C. pneumoniae infection of the vessels may induce a chronic immune response orchestrated by cytokines and mediated by reactive oxygen intermediates. This may result in increased vascular resistance and lead to increased blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Association of HLA-DRB3*0202 and serum IgG antibodies to Chlamydia pneumoniae with essential hypertension in a highly homogeneous population from Majorca (Balearic Islands, Spain)

Zabay¹,

Marco

Soler³

et al. 2005

J Hum Hypertens

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Separate studies investigating the relationship of essential hypertension (EH) with the HLA system and with Chlamydia pneumoniae (C. pneumoniae) infection have given conflicting results. Our aim was to clarify these relationships and determine whether the HLA system and C. pneumoniae infection interact with respect to the risk for EH. An association study (110 essential hypertensives and 107 controls) was conducted in a highly homogeneous population in the Balearic Island of Majorca (Spain). Molecular typing of HLA-B and HLA-DRB and quantification of serum levels of IgG antibodies to C. pneumoniae (sIgGa-Cp) were determined. Student's t-test, v 2 -statistics, logistic regression analysis, and general linear model ANOVA were used for statistical analysis. The results showed that EH was related with HLA-DRB3*0202 in the whole study population, and with levels of sIgGa-Cp463.5 BU/ ml in the group of individuals with sIgGa-Cp430 BU/ml (OR (95% CI) adjusted for obesity, familial history of EH and diabetes ¼ 2.06 (1.07-3.97), P ¼ 0.03, and ¼ 4.60 (1.06-19.90), P ¼ 0.04, respectively). The association between EH and sIgGa-Cp was observed in the DRB3*0202( þ ) individuals, but not in the DRB3*0202(À) subgroup (OR (95% CI) ¼ 11.14 (1.92-64.54), P ¼ 0.004, and ¼ 0.98 (0.22-4.43), P ¼ 0.64, respectively (P of the Mantel-Haenszel test for homogeneity of OR ¼ 0.06)). In our population, EH was positively associated with HLA-DRB3*0202 and with high levels of sIgGa-Cp. Moreover, a significant interaction of DRB3*0202 on the effect of sIgGa-Cp was observed, as the association of EH with these antibodies depended on the presence of DRB3*0202.

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Pro‐inflammatory cytokines in patients with essential hypertension

Abstract: Patients with EH have an altered profile of pro-and anti-inflammatory cytokines, consistent with monocyte activation in the circulation. The importance of these changes for the pathogenesis of EH and/or its secondary complications remains to be elucidated.

Cited by 128 publications

References 30 publications

Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat

Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

Association of HLA-DRB3*0202 and serum IgG antibodies to Chlamydia pneumoniae with essential hypertension in a highly homogeneous population from Majorca (Balearic Islands, Spain)

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