Kinins and Cardiovascular Disease

Carretero, Oscar A.; Yang, Xiao‐Ping; Rhaleb, Nour-Eddine

doi:10.1007/978-1-60761-186-8_12

Cited by 3 publications

(4 citation statements)

References 186 publications

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“…More importantly, ACEi increase circulating and tissue levels of excreted Ac-SDKP multiple fold in humans and animal models [ 38 , 43 , 60 , 61 ]. However, inhibiting ACE results not only in increased Ac-SDKP but also prevents degradation of other vasoactive peptides such as bradykinin (BK) [ 1 , 2 ] and the formation of Ang II. Previously, ACE was believed to have a single catalytic domain, until the cloning of the ACE gene has divulgated that the somatic ACE is made of two homologous protein domains with well-defined catalytic activity and zinc-dependent domains [ 33 , 62 ]; thus, gene silencing of the ACE N-terminal domain by mutation enabled investigation on the role of specific effect of ACE-N while maintaining the ACE-C intact [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin-converting enzyme (ACE) is a vital component of the renin-angiotensin system by not only converting inactive angiotensin (Ang) I to active Ang II but also degrading other endogenous peptides such as bradykinin [ 1 , 2 ]. ACE regulates blood pressure and inflammation, and it mediates other major biological functions such as renal development, hematopoiesis, immune responses, aberrant cell proliferation and migration, and fibrosis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Knockout of ACE-N facilitates improved cardiac function after myocardial infarction

Salehiniya

Peng

Sabbah

et al. 2023

Journal of Molecular and Cellular Cardiology Plus

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knockout of ACE-N facilitates improved cardiac function after myocardial infarction

Salehiniya

Peng

Sabbah

et al. 2023

Journal of Molecular and Cellular Cardiology Plus

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“…Moreover, it has been hypothesized that the virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the RAS (ACE/Ang II /AT 1 R axis), attenuation of ACE2/MasR axis, increased activation of desArg 9 -BK/B 1 receptor pathway, and activation of the complement system including C5a and C5b-9 components [152]. Moreover, Ang (1-7) acting through Mas receptors or Ang (1-9) through AT 2 receptors activates tissue KKS to release kinins, thus providing cardiovascular and renal protection that are mediated by B 2 receptors [2,[153][154][155]. However, a recent clinical study has interestingly reported that COVID-19 patients that received icatibant, a potent B 2 receptor antagonist, experienced improved oxygenation [156]; this is consistent with the role of B 2 receptors in mediating the swelling of soft tissues as a result of excess fluid accumulation [156], and making COVID-19 patients face a life-threatening condition whereby the lungs cannot provide the body's vital organs with enough oxygen [2,11,58,129].…”

Section: Kks Versus Sars-cov2 In Covid-19 Patientsmentioning

confidence: 99%

Role of Kinins in Hypertension and Heart Failure

et al. 2020

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The kallikrein–kinin system (KKS) is proposed to act as a counter regulatory system against the vasopressor hormonal systems such as the renin-angiotensin system (RAS), aldosterone, and catecholamines. Evidence exists that supports the idea that the KKS is not only critical to blood pressure but may also oppose target organ damage. Kinins are generated from kininogens by tissue and plasma kallikreins. The putative role of kinins in the pathogenesis of hypertension is discussed based on human mutation cases on the KKS or rats with spontaneous mutation in the kininogen gene sequence and mouse models in which the gene expressing only one of the components of the KKS has been deleted or over-expressed. Some of the effects of kinins are mediated via activation of the B2 and/or B1 receptor and downstream signaling such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and/or tissue plasminogen activator (T-PA). The role of kinins in blood pressure regulation at normal or under hypertension conditions remains debatable due to contradictory reports from various laboratories. Nevertheless, published reports are consistent on the protective and mediating roles of kinins against ischemia and cardiac preconditioning; reports also demonstrate the roles of kinins in the cardiovascular protective effects of the angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARBs).

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“…Angiotensin-converting enzyme (ACE) is an essential enzyme of the renin–angiotensin system (RAS). Renin first produces angiotensin (Ang) I from angiotensinogen, and then ACE cleaves Ang I releasing the endogenous agonist Ang II (Carretero et al 2009). The ACE protein is a single cell surface zinc metallopeptidase chain, composed of 2 separate and independent catalytic domains.…”

Section: Synthesis and Degradationmentioning

confidence: 99%

Tβ4–Ac-SDKP pathway: Any relevance for the cardiovascular system?

Kassem

Vaid

Peng

et al. 2019

Can. J. Physiol. Pharmacol.

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The last 20 years witnessed the emergence of the thymosin β4 (Tβ4)–N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) pathway as a new source of future therapeutic tools to treat cardiovascular and renal diseases. In this review article, we attempted to shed light on the numerous experimental findings pertaining to the many promising cardiovascular therapeutic avenues for Tβ4 and (or) its N-terminal derivative, Ac-SDKP. Specifically, Ac-SDKP is endogenously produced from the 43-amino acid Tβ4 by 2 successive enzymes, meprin and prolyl oligopeptidase. We also discussed the possible mechanisms involved in the Tβ4–Ac-SDKP-associated cardiovascular biological effects. In infarcted myocardium, Tβ4 and Ac-SDKP facilitate cardiac repair after infarction by promoting endothelial cell migration and myocyte survival. Additionally, Tβ4 and Ac-SDKP have antifibrotic and anti-inflammatory properties in the arteries, heart, lungs, and kidneys, and stimulate both in vitro and in vivo angiogenesis. The effects of Tβ4 can be mediated directly through a putative receptor (Ku80) or via its enzymatically released N-terminal derivative Ac-SDKP. Despite the localization and characterization of Ac-SDKP binding sites in myocardium, more studies are needed to fully identify and clone Ac-SDKP receptors. It remains promising that Ac-SDKP or its degradation-resistant analogs could serve as new therapeutic tools to treat cardiac, vascular, and renal injury and dysfunction to be used alone or in combination with the already established pharmacotherapy for cardiovascular diseases.

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Kinins and Cardiovascular Disease

Cited by 3 publications

References 186 publications

Knockout of ACE-N facilitates improved cardiac function after myocardial infarction

Knockout of ACE-N facilitates improved cardiac function after myocardial infarction

Role of Kinins in Hypertension and Heart Failure

Tβ4–Ac-SDKP pathway: Any relevance for the cardiovascular system?

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