Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease

Schieffer, Bernhard; Bünte, Christoph; Witte, Jana; Hoeper, Kirsten; Böger, Rainer H.; Schwedhelm, Edzard; Drexler, Helmut

doi:10.1016/j.jacc.2004.03.065

Cited by 212 publications

(146 citation statements)

References 41 publications

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“…We have recently demonstrated that inflammatory urine biomarkers also increase in response to acute clamped hyperglycaemia; however, the role of the RAAS in mediating this response and the reversibility of this phenomenon was unknown. We hypothesised that blockade of the RAAS would mitigate the effect of clamped hyperglycaemia on urinary cytokines/chemokines [37][38][39][40].…”

Section: Discussionmentioning

confidence: 99%

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

et al. 2013

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Aims/hypothesis Acute clamped hyperglycaemia activates the renin-angiotensin-aldosterone system (RAAS) and increases the urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Our objective was to determine whether blockade of the RAAS would blunt the effect of acute hyperglycaemia on urinary cytokine/chemokine excretion, thereby giving insights into potentially protective effects of these agents prior to the onset of clinical nephropathy. Methods Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances) and urinary cytokines/ chemokines were measured after 6 h of clamped euglycaemia (4-6 mmol/l) and hyperglycaemia (9-11 mmol/l) on two consecutive days in patients with type 1 diabetes mellitus (n=27) without overt nephropathy. Measurements were repeated after treatment with aliskiren (300 mg daily) for 30 days. Results Before aliskiren, clamped hyperglycaemia increased filtration fraction (from 0.188±0.007 to 0.206±0.007, p=0.003) and urinary fibroblast growth factor-2 (FGF2), IFN-α2 and macrophage-derived chemokine (MDC) (p<0.005). After aliskiren, the filtration fraction response to hyperglycaemia was abolished, resulting in a lower filtration fraction after aliskiren under clamped hyperglycaemic conditions (p=0.004), and none of the biomarkers increased in response to hyperglycaemia. Aliskiren therapy also reduced levels of urinary eotaxin, FGF2, IFN-α2, IL-2 and MDC during clamped hyperglycaemia (p<0.005). Conclusions/interpretation The increased urinary excretion of inflammatory cytokines/chemokines in response to acute hyperglycaemia is blunted by RAAS blockade in humans with uncomplicated type 1 diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

et al. 2013

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“…D-dimer was the only biomarker showing a significant difference between fosinopril intervention (median 0.32 μg/mL, interquartile range 0.22-0.52 μg/mL) and placebo (median 0.29 μg/mL, interquartile range 0.20-0.47 μg/mL, P = .007). From analysis of their data authors concluded that ACE inhibition does not significantly modify major biomarkers of inflammation, hemostasis, and endothelial function, although further studies should have confirmed the possible effect of ACE inhibitors on the fibrinolysis pathway [234]. These really discouraging findings might be specifically related to the ACE inhibitor molecule adopted in the TRAIN study (ie, fosinopril).…”

Section: Perindopril Vs Enalapril (Vs Placebo)mentioning

confidence: 97%

“…Schieffer et al (2004) [234] In patients with CAD and arterial hypertension six to eight weeks after coronary angioplasty, after 3 months of treatment, both enalapril and irbesartan enhanced serum IL-10 levels and reduced serum MMP-9 protein and MMP-9 activity. Only IRB reduced serum IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas ENAL did not.…”

Section: Enalapril (Vs Irbesartan)mentioning

confidence: 99%

“…In a very interesting small randomized study, Schieffer et al [234] assessed, comparing effects of ACEis and ARBs, whether RAS inhibition elicits anti-inflammatory and antiaggregatory effects in patients with CAD and arterial hypertension six to eight weeks after coronary angioplasty. Patients were randomly assigned to either 20 mg enalapril (n=27) or 300 mg irbesartan (n=21) for three months.…”

Section: Perindopril Vs Enalapril (Vs Placebo)mentioning

confidence: 99%

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Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Raimondo¹,

Tuttolomondo²,

Buttà³

et al. 2012

CPD

112

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Abstract:The role of inflammation in cardiovascular disease and in hypertensive disease above all, is complex. Several studies confirm that activation of renin-angiotensin-aldosteron system (RAAS), through increase in the production of angiotensin II (Ang II), is closely related to local vascular inflammation. Over the BP lowering effects of anti-hypertensive treatments, several ancillary effects for every class may be found, distinguishing the various drugs from one another. Given the pro-inflammatory effects of Ang II and aldosterone, agents that interfere with the components of RAAS, such as ACE inhibitors, Angiotensin Recpetor Blockers (ARBs), and mineralocorticoid receptor antagonists (spironolactone or the more selective eplerenone), represent logical therapeutic tools to reduce vascular inflammation and cardiovascular risk, as suggested in large clinical trials in patients with hypertension and diabetes. Regarding ACE inhibitors, actually there is no convincing evidence indicating that ACEi's reduce plasma levels of major inflammatory markers in hypertension models. Lack of evidence concerns especially these inflammation markers, such as fibrinogen of CRP, which are less closely related to atherosclerotic disease and vascular damage and conversely are affected by several more aspecific factors. Results obtained by trials accomplished using ARBs seem to be more univocal to confirm, although to great extent, these is an anti-inflmmatory effect of drugs bocking AT1 receptor. In order to strictly study the effects of blockage of RAAS on inflammation, future studies may explore different strategies by, for example, simultaneously acting on the ACE and the AT1 angiotensin receptors.

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“…Several previous studies have suggested that Ang II via its AT1R plays an important role in triggering inflammatory cardiovascular injury (4,5). Indeed, the cardioprotective effects of AT1R blockade are related to reduced myocardial inflammation in patients with MI (9). Accumulating experimental evidence from AT2R knockout mice or from rats under AT2R agonists further indicates that AT2R, which may be exposed to enhanced Ang II level after AT1R blockade, afford protection against MI-induced cardiac injury (5,10).…”

mentioning

confidence: 98%

Identification of Noncytotoxic and IL-10–Producing CD8+AT2R+ T Cell Population in Response to Ischemic Heart Injury

Curato

Slavić

Dong

et al. 2010

The Journal of Immunology

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Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease

Cited by 212 publications

References 41 publications

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

The effect of aliskiren on urinary cytokine/chemokine responses to clamped hyperglycaemia in type 1 diabetes

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

Identification of Noncytotoxic and IL-10–Producing CD8+AT2R+ T Cell Population in Response to Ischemic Heart Injury

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