Endothelium Dysfunction is known as Non-obstructive vascular dysfunction, where the vascular structure in the body gets disrupted

1. Inventi Rapid: Molecular Pharmacology Vol. 2021, Issue 2
[ISSN 0976-3856]
2021 pmp 33646 © Inventi Journals (P) Ltd
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REVIEW ARTICLE
INTRODUCTION
Molecular pathways play significant role in maintaining
homeostasis and balance in the body. There are various
mechanisms at molecular level which help in maintaining
balance in vascular system of the body. [1] Vascular
endothelium dysfunction is a disease where there is
imbalance of vasodilation and vasoconstriction in the body
and hence disrupting the endothelium in the body resulting
in wide varieties of pathophysiological events, resulting in
wide range of diseases. [2] Diseases such as obesity, chest
pain, myocardial infarction, heart failure or heart attack are
all related pathological diseases associated with vascular
endothelium dysfunction. [3]
Before going into deep understanding of this
pathological event, let us understand, what is an
Endothelium?. Endothelium is tight cell to cell junction
and membrane which separates the tissue and muscular
system from the blood stream in the body. It is because
of its nature that it acts as a barrier between the blood
and the tissue system. It is permeable to certain
substances and non-permeable to others. In other words
it is mainly a barrier. It is also involved in various roles
related to body’s reaction to various events. [4]
1TRM Writers® LLP, Bypass Road, NH-58, Modipuram, Meerut-250110,
Uttar Pradesh, India.
E-mail: devanshm84@gmail.com
*Corresponding author
2Kalka Institute for Research and Advanced Studies. NH-58, Baral Partapur
Bypass Road, Meerut-250103, Uttar Pradesh, India.
Endothelium plays an important role in cardiovascular
homeostasis, platelet aggregation on the walls of blood
vessels, coagulation, inflammatory responses and mainly
either vasodilation of vessels or vasoconstriction of
vessels. [5]
What is a Vascular Endothelium dysfunction? Let’s
understand this before going further deep. Well it is a
condition in which the endothelium loses its control over
the balance or homeostasis in vascular system of the body.
It has wide variety of pathological events related to it
depending upon the site of activity in the body. [6] Like if
vascular endothelium dysfunction is occurring in the
cardiac vessels it results in damaging vasoconstriction,
leading to chest pain. Mainly vascular endothelium
dysfunction results in wide variety of diseases related to
blood vessels in the body without blocking of the blood
vessels itself. Means it’s a non-blockage dependent reason
for wide variety of pathological and cardiovascular events.
It results in high rate of vasoconstriction without blocking
the blood vessels due to aggregation of platelets or
thrombosis. [7] If such events happen in the large blood
vessels of cardiac events, it results in acute or chronic chest
pains. One important understanding regarding the vascular
endothelium dysfunction is that, this pathological event has
been observed to occur in more women as compared to
males. Wide variety of reasons have been investigated
which results in the occurrence and pathogenesis of
vascular endothelium dysfunction. Such as, Smoking,
Stress, Mental tension, imbalance of the periods in women
and other reasons etc.
Endothelium Dysfunction and Importance of Transforming
Growth Factor β (TGF β) and Its Role in the Body and Role of
Tumor Necrosis Factor-Alpha in Endothelium Dysfunction
Devansh Mehta1*, Arabind Kumar2
Abstract: Endothelium dysfunction is a condition in which the endothelium adverse effects are seen and there is disruption of
balanced homeostasis due to endothelium on vascular tree leading to severe vasoconstriction due to increased presence of
vasoconstrictive autacoids. Various diseased condition and pathological conditions are responsible for endothelium dysfunction
such as smoking, obesity and cardiovascular diseases and cardiovascular events. Depending on the site of vascular tree, the
disruption of function of endothelium shows respective effects. Like in large vessels of heart if endothelium dysfunction is
observed it leads to high chest pain condition which is mainly a non-blockage of vessels chest pain condition. As of now various
markers in form of progenitor cells can be used in order to detect endothelium dysfunction in the body or at the site of
pathophysiological conditions. Endothelium dysfunction is mainly a condition where there is imbalance in vasodilation and
vasoconstriction actions of endothelium itself. In Endothelium dysfunction more of vasoconstriction is observed due to
increased presence of vasoconstrictive autacoids at the site of pathophysiological event. It has been widely studied and
understood the role of Endothelium in maintaining the homeostasis of whole vascular system in the body. It releases various
molecules which perform either vasodilation or vasoconstriction on blood vessels in the body. Endothelium is basically a barrier
between the blood and tissue and smooth muscle system in the whole body. Endothelium releases various molecules such as,
Nitric oxide, agents increasing secretion of NO, agent’s responsible s anticoagulants, anti-adhesion agents, agents decreasing the
molecules responsible for increased NO degradation inside the vascular system of the body. Upon endothelium dysfunction all
these actions becomes opposite and there happens decreased secretion or level of Nitric oxide in the body, increased
coagulation of blood vessels in the body, increased degradation of nitric oxide in the body. From the study of endothelium
dysfunction it has been observed and studied the importance of nitric oxide in the body. Nitric oxide is highly important for the
maintenance of homeostasis of the whole vascular tree in the body. Even anticoagulant autacoids are also important agents
responsible for balanced homeostasis in the whole body. They maintain free flow of blood in the vascular system of the whole
body and helps in avoiding coagulation at the site of injury or mascular stress and reverses the coagulation of blood in order to
bring back the homeostasis in the body.
1

2. Inventi Rapid: Molecular Pharmacology Vol. 2021, Issue 2
[ISSN 0976-3856]
2021 pmp 33646 © Inventi Journals (P) Ltd
Published on Web 28/01/2021, www.inventi.in
REVIEW ARTICLE
It has been observed that vascular endothelium
dysfunction is the main reason for wide variety of human
diseases. Like insulin resistance, kidney disturbances, heart
attack, stroke, diabetes, chronic kidney failure and several
viral infectious related diseases. Endothelium is mainly a
cell to cell tight complex membranous barrier in the human
body. [8]
It was once thought as the membrane which acts as a
barrier between tissue and blood vessels having water and
electrolytes. Further studies, on it was taken into
consideration looking at its significance and was found out
to be a major role playing part of the whole vascular tree in
the body. It was also known as once a “cellophane
wrapper”. [9]
During advanced studies since 1980’s, it has now have
been understood to play vital role in cardiovascular system
related pathophysiological events. It plays wide and vital
role in maintaining the homeostasis in the whole body as
both effector and sensory capabilities. It plays a vital role in
blood flow across the body. Hence, any pathological event
related to the flow of blood throughout the body has its
pathogenesis related to the endothelium. And the disease of
endothelium, which is endothelium dysfunction or in other
words, Vascular Endothelium Dysfunction, is main reason
for various damaging events in the body related to the
blood flow across the body. [10]
ROLE OF ENDOTHELIUM IN THE BODY
1. Thrombolysis and thrombosis
2. Coagulant mechanisms
3. Leukocyte and platelet interaction
4. Regulation of vascular tone and relative growth
5. Angiogenesis and Cell proliferation.
1. Thrombolysis and Thrombosis
Endothelium cells or the endothelial cells are involved in
maintaining the homeostasis upon internal or external
disturbances. Such as an injury or any pathophysiological
change which disturbs the normal homeostasis in the body.
If however, Endothelium dysfunction occurs which disrupts
the endothelium system, it results into wide variety of
pathological events and here thrombosis. So, an important
thing to understand is that Endothelium dysfunction
results into thrombosis and results in symptoms in the
body related to thrombosis. Hence, proper medications
such as nitrates, should be used in order to treat
endothelium dysfunction, because if it occurs it will lead to
thrombosis. [11]
2. Coagulation Mechanisms
Coagulation is in simple sense blockage of vessels, due to
coagulation factors. Endothelium plays a vital role in
binding of anticoagulant factors with its receptors thus
maintaining blood flow homeostasis. This mechanism has
been understood so far. So when Endothelium dysfunction
results in it disrupts the homeostasis of binding of
anticoagulant to its receptors resulting in coagulation
within the blood vessels and resultant disruption to a
balanced blood flow within the blood vessels.
3. Leukocyte and Platelet Interaction
The relationship of leukocyte and platelet interaction with
the endothelium was observed and studied around 160
years back, since then many decades after, its relevance has
been understood, where endothelial cells play vital role in
rolling of platelet-leukocyte interaction upon external
stimuli such as mechanical injury, or mechanical stress.
Leukocyte and Platelet Interaction occurs at the walls of
endothelium and results in inflammatory responses, along
with relative series of cascades, leading to pain and
inflammation in the region where any sort of stimuli
disrupts, the normal homeostasis of endothelium and
endothelial cells. [12]
4. Regulation of Vascular Tone and Relative Growth
Endothelium and endothelial cells are source of various
vasodialation and vasoconstriction moieties, which results
in relative vasodilation or vasoconstriction based on
mediators released by the endothelial cells. Dysfunction of
Endothelium system or vascular endothelium dysfunction
disrupts the homeostasis of release of mediators resulting
in balanced vasodilation and balanced vasoconstriction,
leading to various series of cardiovascular events, such as
heart attack or hypertension.
5. Angiogenesis and Cell Proliferation
It has been realized that endothelial cells and endothelium
system results in formation of blood vessels in the body.
They are also involved in development of cell proliferation
and new blood vessels across the body. During vascular
endothelium dysfunction the homeostasis of balance of
newer blood vessels formation results in disruption of
whole vascular system, resulting in related
pathophysiological changes and diseases in the body. [13]
It has been observed that various diseases affect the
endothelium and cause endothelium dysfunction in the
body. Diseases such as cardiovascular diseases, diabetes,
smoking, stress, insulin resistance, etc. cause more or
severe condition of endothelium dysfunction in the body.
Important thing to be understood is that it is non-
obstructive condition of vascular system leading to higher
rate of vasoconstriction due to increased express of
vasoconstrictive autacoids inside the vascular system of the
body. [14, 15]
Endothelium dysfunction can be reversed by using
various drugs used for cardiovascular diseases and role
mainly the statins has been observed significantly in
reversing the diseased condition of Endothelium
Dysfunction in the body. [16]
IMPORTANCE OF TRANSFORMING GROWTH FACTOR β
(TGF β) AND ITS ROLE IN THE BODY
In human body, there are various factors, which control
and run the body in a balanced manner. For body to work
normally, various factors play a major and important role
in order to maintain balance in the whole body. Lots of
growth regulators and growth suppressors, play vital role
in normal day to day homeostasis and running the human
body in better manner. One such important factor is TGF β,
2

3. Inventi Rapid: Molecular Pharmacology Vol. 2021, Issue 2
[ISSN 0976-3856]
2021 pmp 33646 © Inventi Journals (P) Ltd
Published on Web 28/01/2021, www.inventi.in
REVIEW ARTICLE
in other words the transforming growth factor β. TGF β is
important multiplayer growth factor in human body, whose
disruption leads to the development, of various diseases in
the whole human body. It is the growth factor which results
in normal growth of vasculature of whole body. It is one of
the vital growth factors which results in formation of new
blood vessels and repairing the damaged blood vessels
upon any external stress, such as mechanical injury to the
blood vessels.
TGF β is important growth factor which plays multiple
roles in our body. Regarding endothelium, it helps in the
growth of the endothelial cells along with various
mediators and also helps in balanced functioning of
vascular endothelium system.
Upon disruption of this vital growth factor, the
homeostasis in the vasculature gets disrupts and leads to
various pathological events, such as Endothelium
Dysfunction. And as described above, disruption of
endothelium system results in various diseases such
cardiovascular diseases, stroke, diabetes, insulin resistance
and many more.
The importance of mentioning TGF β in Endothelium
Dysfunction is for reason as it can be drug target for the
scientists who would like to develop proper treatment for
endothelium dysfunction. Here, we can see that if we
introduce a molecule in body which helps in disruption of
proliferation and development of TGF β in the body, it can
help in proper treatment of endothelium dysfunction and
treatment of its effects such as cardiovascular diseases,
diabetes, stroke, insulin resistance to name a few.
TGF β plays vital role in whole vasculature system and
its importance for the same has been widely studied and
understood.
Hence, relevance of transforming growth factor β with
relevance to Endothelium Dysfunction is an important part
of our study.
ROLE OF TUMOUR NECROSIS FACTOR-ALPHA IN
ENDOTHELIUM DYSFUNCTION
TNF-α is pro-inhibitory cytokine which has been studied
widely responsible for the pathogenesis of Endothelium
Dysfunction. It has been observed that TNF-α receptor 1
and TNF-α receptor 2, where majorly TNF-α receptor 1 is
responsible for major expression of TNF-α induced
Endothelium Dysfunction. TNF-α causes Endothelium
dysfunction by decreasing the levels of Nitric oxide in the
vascular system along with increased degradation of Nitric
oxide with inducing oxidative stress in the whole body. [19]
It has been observed and widely studied that TNF-α is
mainly responsible for increasing Free radical generation
in the body and also increasing the inflammatory responses
across the whole vascular infrastructure of the body.
Various research’s have been carried out where it has been
observed and tested the role of TNF-α in increasing the
pathophysiological reason for endothelium dysfunction. As
has been already written that in endothelium dysfunction
there is mainly imbalance of vasodilation and
vasoconstriction in the vascular structure of the body, the
TNF-α here leads to increasing the risk factors associated
with the endothelium dysfunction and also increasing the
other pathophysiological events responsible for the over
expression of stress, oxidative stress, inflammatory
responses, damage to the anticoagulation and coagulation
balance in the body and damage to the increased
expression of nitric oxide in the body. It has been observed
and widely tested that TNF-α leads to increased
vasoconstrictive autacoids expression in the body leading
to over expression of endothelium dysfunction along with
its associated pharmacological as well as
pathophysiological events in the whole vascular
infrastructure of the body. Not only this it has been also
widely studied and observed that TNF-α leads to increased
neurodegenerative processes in the body, also increasing
the risks of causing cancer in the whole body. Ever since
the importance of TNF-α has been discovered in the
pathophysiology of wide variety of diseases, it has been
widely studied and its relationship has been understood in
relation to not only Endothelium Dysfunction, but also
Neuro-Degenerative diseases, Nervous system disorder,
Obesity, Diabetes, Insulin resistance, Inflammatory
responses across the body and increased expression of
cancer at various sites in and around the whole body. [17]
TNF-α is mainly involved in the homeostasis of various
systems in the body. And on it’s over expression due to
mechanical stress or internal and external factors it leads
to imbalance cascade of reactions across the body. This is
mainly responsible for the expression of wide variety of
diseases in various systems of the body and leading to
plethora of diseases to the human body. There it has been
selected for the purpose of study, as TNF-α is very
important cytokine to be studied and its role in the
pathogenesis of various diseases.
TNF-α increases the risks factors associated with factors
responsible for the occurrence of Endothelium Dysfunction
in the body, as it leads to high rate of vasoconstriction by
increasing the oxidative stress and decreasing the
expression of Nitric oxide in the vascular infrastructure of
the body. Thus it has been observed that TNF-α plays a
degenerative role in the pathophysiology of Endothelium
Dysfunction. [16-22]
LITERATURE REVIEW OF TNF - α
1. Picchi A et al.,[14] studied the overexpression of TNF-α in
the pathophysiology of Endothelium Dysfunction in
Zucker observed Diabetic rats. The ZOB rats were tested
by injecting various chemicals including TNF-α agent
and were tested using vararious markers for testing the
role TNF-α in the pathophysiology of Endothelium
Dysfunction. From the study by the researcher, it was
confirmed that TNF-α plays a significant role in
increasing the risks factors associated for causing
Endothelium Dysfunction in the body.
2. Iwasima T et al., [15] studied the attenuation activity of
the plant Aroniameranocalpa in the TNF-α induced
human endothelial cell lines. From the experiment, it
was observed that the Aronia berry the plant increased
the attenuation of cytokines induced inflammatory
responses in the body. And it has also been observed
3

4. Inventi Rapid: Molecular Pharmacology Vol. 2021, Issue 2
[ISSN 0976-3856]
2021 pmp 33646 © Inventi Journals (P) Ltd
Published on Web 28/01/2021, www.inventi.in
REVIEW ARTICLE
that the plant Aronia berry helps in attenuation of TNF-
α induced Endothelium Dysfunction in the body.
3. Gao X et al., [16] studied the role played by TNF – α in
increasing the oxidative stress in the body leading to the
causation of endothelium dysfunction in the body. From
the experiment carried out by the researcher, it was
clearly observed that chemicals which were responsible
for decreased expression of TNF-α in the body helped in
lowering the risk factor associated with Endothelium
Dysfunction.
4. Gao X et al., [17] studied whether TNF-α increases the
risks of causing Endothelium Dysfunction via increasing
oxidative stress. From the experiment carried out by the
researcher it was clearly observed that TNF-α plays
significant role in increasing the risks of causing
Endothelium Dysfunction via increasing the oxygen free
radicals in the vascular infrastructure of the body.
LITERATURE REVIEW OF TRANSFORMING GROWTH
FACTOR β (TGF β)
1. Feng W et al., [23] studied the role Transforming growth
factor β which mediates endothelium dysfunction in
rats upon high salt intake. In the experiment the
researcher studied the impact of high salt intake and its
relationship with mediation of tgf-β related to
endothelium dysfunction. From the experiment, it was
completely understood, that how high salt intake results
in Endothelium Dysfunction and related diseases such
as cardiovascular diseases, diabetes and stroke. It is an
important study which helps all of us in understanding
the role of high salt intake in various diseases and
especially endothelium dysfunction.
2. Walshe et al., [24] studied the effect of shear stress in
modulation of TGF β and relative function in
Endothelium. From the experiment, it was completely
understood the role TGF β in normal homeostasis of the
whole vasculature in the body.
3. Schlecht A et al., [25] studied the role played by
proliferation of TGF β in vision loss in experimental
animals. From the study the researcher completely
understood the role played by the Transforming growth
factor in the pathogenesis of vision loss associated with
the Endothelium dysfunction. Hence, the study done by
the researcher is an important study which helps us in
understanding the endothelium dysfunction disease and
its effects at the molecular level in the whole body.
4. Misaki Yamashita [26] studied the Inhibition of
transforming growth factor beta signaling pathway
promotes differentiation of human induced pluripotent
stem cell derived brain microvascular endothelial like
cells. It is a relevant study.
CONCLUSION
Endothelium dysfunction is a non-obstructive disease
where there is no actual blockage of the vascular system,
however, due to imbalance of vasodilation and
vasoconstriction mechanisms, which mainly shifts to
vasoconstriction role, it leads to pain and discomfort in the
body. Both TGF – beta and TNF –alpha play important role
in the pathogenesis of Endothelium Dysfunction. Therefore
it is important to bring their concentration in normal levels
in order to prevent Endothelium Dysfunction.
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[ISSN 0976-3856]
2021 pmp 33646 © Inventi Journals (P) Ltd
Published on Web 28/01/2021, www.inventi.in
REVIEW ARTICLE
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Cite this article as: Devansh Mehta, Arabind Kumar.
Endothelium Dysfunction and Importance of
Transforming Growth Factor β (TGF β) and Its Role in
the Body and Role of Tumor Necrosis Factor-Alpha in
Endothelium Dysfunction. Inventi Rapid: Molecular
Pharmacology, 2021(2):1-5, 2021.
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