A lesson from a saboteur: High‐MW kininogen impact in coronavirus‐induced disease 2019

Colarusso, Chiara; Terlizzi, Michela; Pinto, Aldo; Sorrentino, Rosalinda

doi:10.1111/bph.15154

Cited by 39 publications

(50 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, bradykinin accumulation may explain inflammatory processes, cough and fever. Bradykinin also favours both the complement system and coagulation, mechanisms typical of angioedema, sepsis, and cardiovascular dysfunction, as found in COVID-19 patients (Colarusso, Terlizzi, Pinto, & Sorrentino, 2020).…”

Section: Sex Pulmonary Disease and Covid-19mentioning

confidence: 76%

Sex‐related differences in COVID‐19 lethality

Penna

Mercurio

Tocchetti

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Many countries have been affected by the worldwide outbreak of COVID‐19. Among Western countries, Italy has been particularly hit at the beginning of the pandemic, immediately after China. In Italy and elsewhere, women seem to be less affected than men by severe/fatal COVID‐19 infection, regardless of their age. Although women and men are affected differently by this infection, very few studies consider different therapeutic approaches for the two sexes. Understanding the mechanisms underlying these differences may help to find appropriate and sex specific therapies. Here, we consider that other mechanisms are involved to explain this difference, in addition to the protection attributable to oestrogens. Several X‐linked genes (such as ACE2) and Y‐linked genes (SRY and SOX9) may explain sex differences. Cardiovascular comorbidities are among the major enhancers of virus lethality. In addition, the number of sex‐independent, non‐genetic factors that can change susceptibility and mortality is enormous, and many other factors should be considered, including gender and cultural habits in different countries.

show abstract

Section: Sex Pulmonary Disease and Covid-19mentioning

confidence: 76%

Sex‐related differences in COVID‐19 lethality

Penna

Mercurio

Tocchetti

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Bradykinin is a very potent non-peptide vasoactive, capable of dilating venules through the release of nitric oxide (NO) and increasing vascular permeability through its action on B1 and B2 receptors 9 . The Angiotensin-Converting Enzyme 2 (ACE 2), also known as Kininase II, is one of those responsible for degrading kinins, including bradykinin 10,11 . Sars-CoV-2 binds to ACE 2 receptors to enter the cells 1,11 .…”

Section: Discussionmentioning

confidence: 99%

“…The Angiotensin-Converting Enzyme 2 (ACE 2), also known as Kininase II, is one of those responsible for degrading kinins, including bradykinin 10,11 . Sars-CoV-2 binds to ACE 2 receptors to enter the cells 1,11 . Thus, in COVID-19, because this virus is bound to this receptor, there may be an infra-regulation of ACE 2 receptors, which may result in decreased kinin degradation, thus generating a cascade that may be partially responsible for the emergence of some of the clinical manifestations of COVID-19, among them, angioedema 8 .…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in COVID-19, because this virus is bound to this receptor, there may be an infra-regulation of ACE 2 receptors, which may result in decreased kinin degradation, thus generating a cascade that may be partially responsible for the emergence of some of the clinical manifestations of COVID-19, among them, angioedema 8 . Some studies have even indicated the pharmacological blockade of the Kininogen-Kallikrein-Kinin System (KKKS) as a possible therapy to fight the hyperinflammatory state present in COVID-19 11 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Angioedema, endothelium, ACE2, and bradykinin - interrelationships in COVID-19: a case report

Florêncio¹,

Tenório

Júnior³

et al. 2020

Medicina (Ribeirão Preto)

View full text Add to dashboard Cite

COVID-19 is a new disease, whose several atypical clinical manifestations began to be observed with the evolution of the pandemic, and have been investigated to understand the pathophysiology of the disease. In this article, the objective is to describe a case of angioedema in COVID-19, considered an atypical manifestation, and rarely described in the literature. The case is of a 55-year-old patient who sought medical attention for a complaint of intermittent fever for four days. On the seventh day, he manifested angioedema in the left zygomatic projection and the right subpalpebral region. The patient had no history of angioedema earlier in life. The following day, he presented a regression of the angioedema concerning the previous day. After this period, the patient progressed well and became asymptomatic. The RT-PCR laboratory test performed on the first days of manifesting symptoms was positive for SARS-CoV-2. We correlate the onset of angioedema with the possible endotheliitis present in the disease, which has been evidenced by the observation of severe endothelial injury associated with the intracellular presence of the virus in several histopathological studies of patients with COVID-19. Also, possible deregulation of the Kininogen-Kallikrein-Kinin System (KKKS) could explain this manifestation, as SARS-CoV-2 binds to the ACE2 receptor, which is responsible for degrading kinins, such as bradykinin.

show abstract

“…The CS is involved in inflammation and in coagulation: when sufficient amounts of FXII are activated, FXIIa also activates FXI (to FXIa), and the intrinsic (or contact) coagulation pathway can start, leading to subsequent thrombin activation and fibrin formation. KAL can influence the fibrinolytic pathway by activating plasminogen into plasmin, thus leading also to fibrin degradation (23). D-dimer is a soluble fibrin degradation product deriving from the plasmin-mediated degradation of cross-linked fibrin: it can therefore be considered a biomarker of concomitant activation of both coagulation and fibrinolysis (24).…”

Section: The Role Of the Contact System In The Pathophysiology Of Covmentioning

confidence: 99%

Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key?

et al. 2020

View full text Add to dashboard Cite

To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein-Kinin (KKS), the Coagulation/Fibrinolysis and the Renin-Angiotensin (RAS) Systems. We investigated the role of the mediators involved. CS consists of Factor XII (FXII) and plasma prekallikrein (complexed to highmolecular-weight kininogen-HK). Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK. BK binds to B2-receptors, mediating vascular permeability, vasodilation and edema. B1-receptors, binding the metabolite [des-Arg 9 ]-BK (DABK), are up-regulated during infections and mediate lung inflammatory responses. BK could play a relevant role in COVID-19 as already described for other viral models. Angiotensin-Converting-Enzyme (ACE) 2 displays lung protective effects: it inactivates DABK and converts Angiotensin II (Ang II) into Angiotensin-(1-7) and Angiotensin I into Angiotensin-(1-9). SARS-CoV-2 binds to ACE2 for cell entry, downregulating it: an impaired DABK inactivation could lead to an enhanced activity of B1-receptors, and the accumulation of Ang II, through a negative feedback loop, may result in decreased ACE activity, with consequent increase of BK. Therapies targeting the CS, the KKS and action of BK could be effective for the treatment of COVID-19.

show abstract

A lesson from a saboteur: High‐MW kininogen impact in coronavirus‐induced disease 2019

Cited by 39 publications

References 55 publications

Sex‐related differences in COVID‐19 lethality

Sex‐related differences in COVID‐19 lethality

Angioedema, endothelium, ACE2, and bradykinin - interrelationships in COVID-19: a case report

Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key?

Contact Info

Product

Resources

About