Role of tissue kallikrein in the cardioprotective effects of ischemic and pharmacological preconditioning in myocardial ischemia

Griol-Charhbili, Violaine; Messadi-Laribi, E; Bascands, Jean-Loup; Heudes, Didier; Meneton, Pierre; Giudicelli, Jean‐François; Alhenc-Gélas, François; Richer, Christine

doi:10.1096/fj.04-3508fje

Cited by 73 publications

(92 citation statements)

References 43 publications

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“…This compensatory phenomenon is also observed by other researchers in mouse models. 18,22,23 The exact role of the B1R in the diabetic kidney warrants further investigation. Apart from biochemical improvement, there was also histological improvement, and reduced macrophage infiltration and interstitial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Additive renoprotective effects of B2-kinin receptor blocker and PPAR-γ agonist in uninephrectomized db/db mice

Tang

Chan

Leung

et al. 2011

Laboratory Investigation

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We recently showed that the bradykinin B2 receptor (B2R) blocker icatibant (Icat) and the peroxisome proliferatoractivated receptor-g agonist rosiglitazone (Ros) exerted anti-inflammatory effects in renal tubular cells exposed to a diabetic milieu. This study aims to explore whether these effects can be translated to an experimental model of type 2 diabetic nephropathy (DN). db/db mice and their nondiabetic db/m littermates underwent sham operation or uninephrectomy (Unx) at 10 weeks and received vehicle (Veh), metformin (Met), Icat, Ros, or Icat plus Ros for 8 weeks before killing. Among the db/db group with Unx, mice that received Icat or Ros had significantly lower serum creatinine and albuminuria, which was further reduced when Icat and Ros were given in combination. These beneficial effects were not observed in the Met group that achieved similar glycemic control as Ros-treated animals. Likewise, the severity of reactive glomerular and proximal tubular hypertrophy, glomerulosclerosis, interstitial injury, cortical F4/80 and a-smooth muscle actin immunostaining, and CCL-2, ICAM-1 and TGF-b overexpression were all attenuated by Icat and Ros, and these effects were enhanced when both agents were combined. Immunohistochemical staining confirmed the proximal tubular expression of CCL-2 (inflammation) and TGF-b (fibrosis). Treatment with Icat was associated with decreased B2R, but increased, B1R expression, which was exaggerated in Unx animals. At the signaling level, Icat and Ros reduced extracellular signal-regulated kinase 1/2 and STAT1 activation, respectively. Our results suggest a deleterious role of the kallikrein-kinin system in murine-accelerated DN, which can be ameliorated by the B2R blocker Icat and enhanced by the addition of Ros. This calls for further evaluation of this novel therapeutic approach in more animal models of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Additive renoprotective effects of B2-kinin receptor blocker and PPAR-γ agonist in uninephrectomized db/db mice

Tang

Chan

Leung

et al. 2011

Laboratory Investigation

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“…Intact kinins bind to the kinin B2 receptor and activate second messengers such as nitric oxide (NO), cGMP, prostacyclin and cAMP, to produce a broad spectrum of biological effects [10]. A study using kallikrein-or kinin B2 receptor-deficient mice showed that both tissue kallikrein and the B2 receptor play an important role in cardioprotection during ischemic injury [11]. Moreover, a recent report demonstrated that expression of tissue kallikrein in transgenic mice reduces intramyocardial inflammation and oxidative stress in experimental diabetic cardiomyopathy [12].…”

Section: Introductionmentioning

confidence: 99%

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

Yao

Yin

Shen

et al. 2007

Regulatory Peptides

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We investigated the effect of tissue kallikrein infusion on cardiac protection at acute and sub-acute phases after myocardial infarction (MI). Immediately after MI, rats were infused with purified tissue kallikrein, with or without icatibant (a kinin B2 receptor antagonist). Intramyocardial injection of kallikrein reduced myocardial infarct size and inhibited cardiomyocyte apoptosis at 1 day after MI associated with increased nitric oxide levels, Akt and glycogen synthase kinase-3β phosphorylation and decreased caspase-3 activation. Kallikrein infusion for 7 days improved cardiac function, normalized left ventricular wall thickness and decreased monocyte/macrophage infiltration in the infarct heart. Kallikrein treatment reduced NADH oxidase expression and activity, superoxide formation and malondialdehyde levels, and reduced MAPK and Iκ-Bα phosphorylation, NF-κB activation and MCP-1 and VCAM-1 expression. Kallikrein's effects were all blocked by icatibant. These results indicate that kallikrein through kinin B2 receptor activation prevents apoptosis, inflammation and ventricular remodeling by increased nitric oxide formation and suppression of oxidative stress-mediated signaling pathways.

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“…In addition, several studies have suggested that agonism of the B1R may have opposite effects from agonism of the B2R on the severity of I/R injury (23). Although expression of the B1R is much less than that of B2R in the kidney and heart of WT mice, it is markedly induced in B2R-null mice (14,15), and expression of both receptors increases in I/R injury (24). However, whether they act synergistically or antagonistically and whether or not the kallikrein-kinin system has net protective effects in I/R injuries remain unanswered questions.…”

mentioning

confidence: 99%

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Kakoki

McGarrah

Kim

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

119

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To explore the role of the kallikrein-kinin system in relation to ischemia/reperfusion injury in the kidney, we generated mice lacking both the bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1 ؊/ ؊/Bdkrb2 ؊/؊ ) by deleting the genomic region encoding the two receptors. In 4-month-old mice, blood pressures were not significantly different among B1RB2R-null, B2R-null (Bdkrb2 ؊/؊ ), and WT mice. After 30 min of bilateral renal artery occlusion and 24 h of reperfusion, mortality rates, renal histological and functional changes, 8-hydroxy-2 -deoxyguanosine levels in total DNA, mtDNA deletions, and the number of TUNEL-positive cells in the kidneys increased progressively in the following order (from lowest to highest): WT, B2R-null, and B1RB2R-null mice. Increases in mRNA levels of TGF-␤1, connective tissue growth factor, and endothelin-1 after ischemia/reperfusion injury were also exaggerated in the same order (from lowest to highest): WT, B2R-null, and B1RB2R-null. Thus, both the B1 and B2 bradykinin receptors play an important role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal ischemia/reperfusion injury.hypoxia ͉ mitochondria ͉ oxidative stress I schemic tissue injuries, including stroke, myocardial infarction, and ischemic acute renal failure, are devastating complications in patients with hypertension, diabetes, atherosclerosis, and senescence. In organ transplantation, damage to allografts during any ischemic period before the transplant markedly influences short-term and long-term graft function and outcome (1). Furthermore, although reoxygenation after ischemia is essential for cell survival, damage also develops during the reperfusion period. Previous studies have shown that acute ATP depletion, intracellular Ca 2ϩ accumulation, and increased generation of reactive oxygen species by mitochondria all play important roles in the pathogenesis of ischemia/reperfusion (I/R) injury (2).Angiotensin-I-converting enzyme (ACE) inhibitors (ACEIs) reduce not only chronic cardiovascular remodeling after ischemia but also acute tissue injury caused by I/R in the heart (3), lung (4), liver (5), and kidneys (6, 7). Several observations indicate that the beneficial effects of ACEIs in the acute phase are mainly due to activation of the bradykinin nitric oxide (NO) cascade as a result of inhibition of the inactivation of bradykinin, rather than due to suppression of angiotensin II formation. Thus, ACEIs are much more effective than angiotensin type I receptor antagonists in protecting against I/R (8-10), and bradykinin B2 receptor (B2R) antagonists and NO synthase blockers markedly attenuate the protective effects of ACEIs (8, 9, 11).Bradykinin and lysyl-bradykinin (kallidin) are generated from kininogens by the kallikreins and some other serine proteases. ACE, which is a carboxydipeptidase, inactivates both peptides by removing two amino acids from their carboxyl termini. In mammals, at least two receptors have been identified: the bradykinin B1 receptor (B...

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Role of tissue kallikrein in the cardioprotective effects of ischemic and pharmacological preconditioning in myocardial ischemia

Cited by 73 publications

References 43 publications

Additive renoprotective effects of B2-kinin receptor blocker and PPAR-γ agonist in uninephrectomized db/db mice

Additive renoprotective effects of B2-kinin receptor blocker and PPAR-γ agonist in uninephrectomized db/db mice

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

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