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

Yao, Yuyu; Yin, Hang; Shen, Bo; Chao, Lee; Chao, Julie

doi:10.1016/j.regpep.2006.11.020

Cited by 48 publications

(40 citation statements)

References 32 publications

(31 reference statements)

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“…The antiapoptotic effect of the KKS was also demonstrated in vivo [24,[42][43][44]. In rats, immediate tissue kallikrein infusion after myocardial infarction reduced myocardial infarct size and inhibited cardiomyocyte apoptosis along with decreased p38 MAPK phosphorylation [44]. Moreover, BK infusion in Dahl salt-sensitive rats fed with high-salt diet and tissue kallikrein infusion in rats with gentamicininduced nephrotoxicity ameliorated tubular cell apoptosis [24,42], which was associated with the attenuation of increased p38 MAPK phosphorylation and of decreased Akt phosphorylation, respectively.…”

Section: Discussionmentioning

confidence: 92%

“…In addition, stretch-induced apoptosis in cultured alveolar type II cells was inhibited by BK [33]. The antiapoptotic effect of the KKS was also demonstrated in vivo [24,[42][43][44]. In rats, immediate tissue kallikrein infusion after myocardial infarction reduced myocardial infarct size and inhibited cardiomyocyte apoptosis along with decreased p38 MAPK phosphorylation [44].…”

Section: Discussionmentioning

confidence: 99%

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Local kallikrein–kinin system is involved in podocyte apoptosis under diabetic conditions

et al. 2011

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The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Local kallikrein–kinin system is involved in podocyte apoptosis under diabetic conditions

et al. 2011

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“…Modification of MSCs with the TK gene could provide enhanced cardiac protection possibly by TK's ability to activate the kinin B2 receptor, either dependent or independent of kinin formation, thereby attenuating myocardial injury through Akt signaling and nitric oxide production. 15 Although the contribution of kinins to the protective effects of TK-MSCs was not investigated in the present study, Koch et al showed that transgenic rats overexpressing TK have increased basal kinin levels that may be responsible for the improvement in cardiac function and remodeling in these rats after MI. 35 Furthermore, while no difference in infarct size and cardiac function was observed between the TK-MSC and GFP-MSC MI groups 1 day after MI, the effects of TK-MSCs on inflammation and apoptosis may lead to improvement in these areas over a longer period of time.…”

Section: Tk-mscs Promote Neovascularization In the Myocardium At 2 Wementioning

confidence: 64%

“…13, 14 Moreover, TK suppressed cardiomyocyte apoptosis in vitro and in vivo by inhibiting oxidative stress and activating Akt-mediated signaling pathways. 15 TK also attenuated cardiac inflammation, hypertrophy and fibrosis, and increased nitric oxide formation in rats after MI. 15 We demonstrated that administration of TK-modified MSCs in the kidney protected against ischemia-induced renal injury by suppression of apoptosis and inflammation.…”

mentioning

confidence: 85%

“…15 TK also attenuated cardiac inflammation, hypertrophy and fibrosis, and increased nitric oxide formation in rats after MI. 15 We demonstrated that administration of TK-modified MSCs in the kidney protected against ischemia-induced renal injury by suppression of apoptosis and inflammation. 16 Therefore, in the present study we investigated the potential beneficial effects MSCs genetically hronic heart failure induced by myocardial infarction (MI) leads to a loss of cardiac tissue and impairs left ventricular function.…”

mentioning

confidence: 85%

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Tissue Kallikrein-Modified Mesenchymal Stem Cells Provide Enhanced Protection Against Ischemic Cardiac Injury After Myocardial Infarction

Gao

Bledsoe

Yin

et al. 2013

Circ J

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Background: Genetically modified mesenchymal stem cells (MSCs) are a promising approach to the treatment of cardiac injury after myocardial infarction (MI). Methods and Results:Rat MSCs were transduced with adenovirus containing human tissue kallikrein (TK) gene (TK-MSCs), and they secreted human TK into culture medium. Cultured TK-MSCs were more resistant to hypoxiainduced apoptosis and exhibited reduced caspase-3 activity compared to control GFP-MSCs. The effect of TK-MSC injection on cardiac injury was evaluated in rats at 1 and 14 days after MI. At 1 day after MI, human TK expression in the myocardium was associated with improved cardiac function and decreased inflammatory cell accumulation, proinflammatory gene expression and apoptosis. The beneficial effect of TK-MSCs against apoptosis was verified in cultured cardiomyocytes, as TK-MSC-conditioned medium suppressed hypoxia-induced apoptosis and caspase-3 activity, and increased Akt phosphorylation. At 2 weeks after MI, TK-MSCs improved cardiac function, decreased infarct size, attenuated cardiac remodeling, and promoted neovascularization, as compared to GFP-MSCs. Furthermore, the TK-MSC-conditioned medium, containing elevated vascular endothelial growth factor levels, stimulated the proliferation, migration and tube formation of cultured human endothelial cells. Conclusions:Our results indicate that TK-modified MSCs provide enhanced protection against cardiac injury, apoptosis and inflammation, and promote neovascularization after MI, leading to cardiac function improvement. (Circ J 2013; 77: 2134 -2144

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The other possible mechanism of the benefits of RAAS inhibition in the athogenesis of COVID‐19

Gupta

Patel

Gupta³

2020

Clinical Cardiology

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Letter to the Editor, We read with interest the meta-analysis of association of angiotensinconverting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) with the risk and severity of COVID-19. 1 Another possible explanation of the beneficial effect of renin-angiotensin-aldosterone system (RAAS) inhibition on the severity of COVID-19 is via increasing tissue kallikrein and upregulating ACE-2 receptors.It is proven that tissue kallikrein prevents apoptosis and ventricular remodeling after myocardial infarction. 2 Since organ injury determines mortality in hypertensive patients infected with SARS-CoV-2, increased bradykinin levels induced by ACE inhibition may provide more protection than harm in cardiovascular disease (CVD)-comorbid COVID-19 patients.Animal models of infection with SARS-CoV showed that ACE-2 downregulation resulted in pro-inflammatory responses, including lung injury and impairment of cardiac contractility. 3 If SARS-CoV-2 infections progress like SARS-CoV, the virus may deteriorate a patient's condition by lowering ACE-2 expression and by decreasing the degradation of angiotensin II (Ang-II). Overabundance of Ang-II has multiple deleterious cardiovascular consequences including elevating blood pressure, cardiomyocyte apoptosis, cardiac infiltration by macrophages, and secretion of pro-inflammatory cytokines. Secondly, less ACE-2 reduces the formation of angiotensin (1-7) (Ang 1-7) and its CVD-protective vasodilatory, anti-inflammatory, antifibrillatory, and antiproliferatory effects. 4 In particular, Ang 1-7 can diminish Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-α), macrophage infiltration, vascular cell adhesion protein.Ferrario and co-workers have showed that ACEI caused a 1.8-fold rise of plasma Ang 1-7 concentrations and an approximately 25% increase of ACE-2 expression in the left ventricle. 5 Thus, the usage of ACE inhibitors and ARBs may have a potential benefit in preventing COVID-19-triggered organ damage via its upregulation of Ang 1-7, depletion of Ang-II, and upregulating ACE-2 receptors.

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

Cited by 48 publications

References 32 publications

Local kallikrein–kinin system is involved in podocyte apoptosis under diabetic conditions

Local kallikrein–kinin system is involved in podocyte apoptosis under diabetic conditions

Tissue Kallikrein-Modified Mesenchymal Stem Cells Provide Enhanced Protection Against Ischemic Cardiac Injury After Myocardial Infarction

The other possible mechanism of the benefits of RAAS inhibition in the athogenesis of COVID‐19

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