Angiotensin converting enzyme 2
Angiotensin
converting enzyme 2, or ACE2, is an exopeptidase expressed primarily by
vascular endothelial cells in the heart and kidneys, but also in respiratory
epithelia[1] and in the gastrointestinal tract. It is the target of several
coronaviruses, including SARS-CoV and SARS-CoV-2.
2
Biochemistry
ACE2
is a transmembrane metallocarboxypeptidase composed of 805 amino acids. Zinc
and chloride ions act as cofactors. The extracellular region consists of two
domains, a zinc metallopeptidase domain and a C-terminal collectrin homology
domain. The enzyme exhibits homology to angiotensin converting enzyme (ACE).
ACE2
is encoded by the ACE2 gene on the X chromosome (gene locus Xp22.2). In
addition to being expressed as a transmembrane protein, a soluble form exists
in serum.
3
Function
ACE2
cleaves angiotensin II into angiotensin (1-7), which has anti-inflammatory and
lung protective effects via MAS and AT2 receptors.
4
Clinical
4.1
Infectiology
ACE2
serves as a major entry point for some coronaviruses. The pathogens bind to the
enzyme with their spike proteins and enter the host cell by subsequent
fusion.[2] ACE2 expression increases from the pharynx to the alveoli. In
addition, SARS-CoV-2 is thought to have a higher affinity for ACE2 than
SARS-CoV. This would explain more rapid and effective viral transmission in the
COVID-19 pandemic.
Patients
taking drugs that increase the expression of ACE2 - for example, ACE inhibitors
or sartans, may be at higher risk of infection and should be switched to
calcium antagonists, according to some authors.[3][4] In contrast, the relevant
professional societies see no need for action at this time (4/2020).[5][6]
4.2
Pharmacology
Human
recombinant ACE2 (APN01) is an experimental therapeutic approach being tested
in acute respiratory distress syndrome (ARDS) and pulmonary hypertension.[7]
Furthermore, it is currently (2020) being tested for the treatment of
COVID-19.[8][9]
5
Sources
1.
jump up ↑ Hong Peng Jia et al. ACE2 Receptor Expression and Severe Acute
Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human
Airway Epithelia, J Virol. 2005 Dec; 79(23): 14614-14621, retrieved 2020 Mar
27.
2.
jump up ↑ Kuba K et al. A crucial role of angiotensin converting enzyme 2
(ACE2) in SARS coronavirus-induced lung injury, Nat Med. 2005 Aug;11(8):875-9.
epub 2005 Jul 10, retrieved 2020 Mar 30.
3.
jump up ↑ Zheng Y et al. COVID-19 and the cardiovascular system, Nat Rev
Cardiol (2020), retrieved 30 Mar 2020.
4.
jump up ↑ Fang, L. et al. Are patients with hypertension and diabetes mellitus
at increased risk for COVID-19 infection?, The Lancet, March 2020, retrieved
27/03/2020.
5.
jump up ↑ ESC Position Statement of the ESC Council on Hypertension on ACE
Inhibitors and Angiotensin Receptor Blockers, retrieved March 27, 2020.
6.
jump up ↑ The Renal Association, UK position statement for patients: novel
corona virus infection and the use of blood pressure medications. retrieved
03/27/2020.
7.
jump up ↑ Zhang H, Baker A Recombinant human ACE2: acing out angiotensin II in
ARDS therapy, Crit Care. 2017 Dec 13;21(1):305, retrieved 2020 Mar 30.
8.
jump up ↑ Zhang H et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2
receptor: molecular mechanisms and potential therapeutic target, Intensive Care
Med. 2020 Apr;46(4):586-590, retrieved 2020 Mar 30.
9.
upjump ↑ clinicaltrials.gov APN01, retrieved 03/30/2020.
Mar
19, 2020May 7, 2020
CoViD-19
and ACE inhibitors.
The
disease is often moderate or even asymptomatic. However, severe courses can
occur, usually manifesting as pneumonia. In some of the seriously ill patients,
severe cardiovascular damage is also observed.
For
people with heart disease, the disease - which is caused by the SARS-CoV-2
virus - thus appears to be particularly dangerous.
Angiotensin-converting
enzyme 2 (ACE2) plays a major role in the body's water balance. ACE inhibitors
lower blood pressure and reduce afterload - which also makes them very useful
in treating heart failure disease.
ACE2
are particularly abundant in the heart and lungs. Currently, attention is
focused on this enzyme because ACE2 has been identified as a functional
receptor for the coronaviruses SARS-CoV and SARS-CoV-2.
It
appears that the amount of ACE2 increases by taking ACE2 inhibitors in
response. Thus, the body responds to inhibition of these receptors by
increasing potential docking sites.
It
has not yet been proven whether this mechanism promotes or exacerbates the
disease!
Up-regulating
ACE2 may also have benefits: The enzyme protects the heart and vasculature by
cleaving angiotensin II-which promotes hypertension, edema, and tissue
damage-and thereby inactivating it.
In
SARS-CoV infection, ACE2 is downregulated as an antiviral protective measure:
Angiotensin II can then promote severe tissue damage during infection. ACE
inhibitors and sartans could therefore be helpful because they slow down
angiotensin II formation or block the corresponding receptor, respectively ...
It
is a fact that special attention is paid to patients with underlying
cardiovascular disease in connection with covid-19 disease. Recently, experts
from the U.S. Cardiac Society (ACC) considered the viral epidemic from a
cardiology perspective in an official letter of recommendation. The society
makes nine recommendations for managing the coronavirus epidemic.
The
experts recommend that "consistent use of guideline-based therapy with
plaque-stabilizing agents (statins, beta blockers, ACE inhibitors, ASS)
provides additional protection for cardiac patients, and such treatment should
be tailored to individual patients." Accordingly, these experts do not
currently consider ACE inhibitors to be critical.
That
this is a preliminary assessment is reflected in point 9 of the recommendation:
here, the experts point out that little is currently known about coronavirus
and physicians should be prepared for new recommendations as more information
becomes available.
Source:
www.pharmazeutische-zeitung.de/
What Teaches Us the Autoimmune Theory?
The members of the
family Coronaviridae, a
monophyletic cluster in the order Nidovirales, are enveloped, positive
stranded RNA viruses of three classes of vertebrates: mammals
(corona -and toroviruses), birds (coronaviruses) and fish (bafiniviruses).
Virions are spherical, 120–160 nm across (Coronavirinae),
bacilliform, 170–200×75–88 nm (Bafinivirus) or found as a
mixture of both, with bacilliform particles characteristically bent into
crescents (Torovirus). The particles are typically decorated with
large, club- or petal-shaped surface projections (the “peplomers” or “spikes”),
which in electron micrographs of spherical particles create an image
reminiscent of the solar corona. This inspired the name of the “true” coronaviruses (now
grouped in the subfamily Coronavirinae), which was later adopted for the whole family. Nucleocapsids are
helical and can be released from the virion by treatment with detergents.
Whereas the coronavirus nucleocapsid appears to be loosely-wound, those of the Torovirinae are
distinctively tubular.
In terms of genome size and
genetic complexity, the Coronaviridae are
the largest RNA viruses identified
so far, rivaled only by the okaviruses,
large nidoviruses of invertebrates assigned to the family Roniviridae. Replication has been studied in detail only
for coronaviruses, but the limited data available for toro- and bafiniviruses
suggest that the latter viruses use essentially similar strategies. Virions
attach to dedicated host cell surface
receptors via their spikes and release their genome into the
target cell via fusion of the viral envelope with the plasma membrane and/or
the limiting membrane of an endocytic vesicle. The entire replication cycle
takes place in the cytoplasm and involves the production of full-length and
subgenome-sized (sg) minus-strand RNA intermediates with the viral genome serving
both as mRNA for the replicase polyproteins and as a template for minus-strand
synthesis. RNA
synthesis is catalyzed by an as yet poorly characterized
replication–transcription complex, composed of viral and host proteins and
associated (at least in coronaviruses) with an interconnected network of
modified intracellular
membranes and double-membrane vesicles that are presumably
endoplasmic reticulum (ER)-derived.
The conclusion is that Corona
viruses are wide spread in nature, affect animals and humans. They enter the
cells through a receptor ACE 2 which is found on endothelial cells of blood
vessels, which is amongst all also responsible for regulating blood pressure.
So if we consume those
animals our immune system gets in contact with those receptors which are big
protein molecules and our immune system produces antibodies against those
receptors. And this way of thinking could explain the origin of essential hypertension.
We know that ACE-blockers
are an antihypertensive therapy because they block the converting of angiotensin
I into angiotensin II. The angiotensin II formed interacts with angiotensin II
receptors (AT receptors). Activation of the AT1 receptor can cause contraction
primarily in blood vessels. In the kidney, constriction of efferent blood
vessels keeps the glomerular filtration rate as constant as possible. In the
adrenal gland, angiotensin II stimulates aldosterone and epinephrine release,
and in the pituitary gland, a release of vasopressin. The sensation of thirst
is also attributed to acute stimulation of AT1 receptors in the hypothalamus.
Chronic stimulation of the AT1 receptor, on the other hand, leads to
stimulation of mitogenic effects and thus, for example, to hypertrophy of the
heart. Acute and chronic effects of angiotensin II on the AT1 receptor can be
suppressed indirectly by ACE inhibitors and directly by AT1 receptor antagonists
(sartans) or saralasin.
Angiotensin II also shows a high affinity for AT2 receptors. The
importance of these receptors in the effects mediated by angiotensin II,
however, is controversial. Animal studies in mice provided evidence that the
action at AT2 receptors has an attenuating influence on the effects at AT1
receptors in the sense of counteracting them.
Angiotensinamide, a
derivative of angiotensin II, is a cardiostimulatory and blood
pressure-increasing drug.
Through the knowledge
which we acquired reading “The Theory Of Autoimmunity” we suspect that anti ACE
2 receptor antibodies could activate the ACE 2 receptor thus causing essential
arterial hypertension and this is a question that affects major part of the
population on Earth.
For more: https://www.amazon.com/dp/B09NGSF57G/ref=mp_s_a_1_2?crid=PDMS10VW4812&keywords=tanya+guleria&qid=1639247917&sprefix=tanya+gul%2Caps%2C178&sr=8-2
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