Abstract
Atherosclerosis was thought of as a degenerative, progressive
disease, affecting the elderly, and causing symptoms by its
mechanical effects on blood flow, especially in the small
arteries supplying the myocardium and brain. Thus, the
treatment has been surgical for a long time and focused on the
largest and most visible or symptomatic lesions, coupled with a
belief that there was little likelihood of medical management
affecting such an end stage process. Scientific understanding of
atherogenesis is still developing. However, the mechanisms by
which many of the newer variants exert their influence remain
unknown. Recent research into the cellular and molecular
events causing the development and progression of
atherosclerosis, prompted by careful descriptive studies of the
underlying pathology, has shown that atherosclerosis is a
dynamic, inflammatory process that is notably modifiable
Support for this view comes from clinical trials of lipid lowering
agents, especially the “statins”, which have shown minor
effects on the size of existing lesions, but major decrease in
clinical events caused by plaque rupture, causing a beneficial
stabilizing effect on plaque composition. A better
understanding of the molecular and cellular basis of
atherosclerosis will automatically lead to the design of better
diagnostic and therapeutic methods. The aim of this review is
to summarize current understanding of the pathogenesis and
progression of atherosclerosis with risk factors and the leading
causes of it. The review also summarized the newly techniques
and lines of treatment. We didn’t forget to talk about
protective medicine and the recent studies talking about
traditional medicine in the protection of atherosclerosis.
Introduction
,The endothelium maintains vascular tone and blood fluidity
with minimal expression of pro-inflammatory factors under
normal homeostatic conditions. Healthy human arteries
have a tri-laminar structure. The tunica intima is the inner
layer of endothelial cells lining the lumen called the
endothelium. The endothelium is in direct contact with
blood flow and arterial endothelial cells have many highly
regulated mechanisms that are of vital role in maintaining
vascular homeostasis. Despite it is often described as a
monolayer, in human adults it is a more complex and
heterogeneous structure containing some smooth muscle
cells and collagen. It is bound from the outside by internal
elastic lamina, which separates the intima from the tunica
media. The media contains many layers of smooth muscle
cells. In large elastic arteries smooth muscle cells are
arranged in a concentric manner within an extra cellular
matrix rich in elastin which helps store kinetic energy
needed for the transmission of pulsatile flow. The media is
bound on the outside by an external elastic lamina that
separates the media from the adventitia. The adventitia
consists of fibroblasts, mast cells, and a matrix which
contains collagen and proteoglycans. The normal, healthy
endothelium is the major regulator of vascular homeostasis
keeping the balance between vasodilation and
vasoconstriction, inhibition and stimulation of smooth
muscle cell proliferation and migration, and thrombogenesis
and fibrinolysis. The first insight to the importance of the
endothelium in vasomotor modulation started from animal
experiments in the 1980s. It became evident that the
endothelium is an active paracrine, endocrine and autocrine
organ which has the ability to receive various degrees of
stimulation subsequently. a spectrum of endothelial
disturbance exists that depends on the physiological, or
, pathophysiological conditions. Its main vaso regulatory
functions include 1- Secretion of nitric oxide, a strong
vasodilator simply identified as endothelium derived relaxing
factor. Other endothelium-derived vasodilators are
prostacyclin and bradykinin both of which also inhibit
platelet aggregation 2- Secretion of vasoconstrictor
substances such as endothelin and angiotensin II.
Angiotensin II is pro-oxidant, and both stimulate smooth
muscle cell proliferation within the intimal layer. In normal
vascular physiology, nitric oxide is the most important factor
in maintaining the vascular wall in a quiescent state by
inhibiting inflammation, cellular proliferation, and
thrombosis. This is achieved through the expression of some
protective genes (A20, B-cell lymphoma 2 gene) that down-
regulate the expression of transcription factor nuclear factor
since activation of nuclear factor triggers endothelial
activation and makes the endothelium more susceptible to
apoptosis. Nitric oxide limits oxidative phosphorylation in
the mitochondria as well. Laminar shear stress is probably
the major factor that keeps this quiescent, nitric oxide-
dominated, endothelial phenotype with minimal or no
expression of proinflammatory factors.(1)
Early vascular lesions are composed of focal changes
superimposed on the diffusely thickened intima. Grayish
gelatinous lesions are focal areas of excessive fluid build-up
in the intima. Fatty streaks are areas of lipid build-up that
result in insignificant additional thickening of the intimal
layer. The lipids usually have an intracellular localization but
may be partially extracellular. The lipid-laden foam cells are
the macrophages derived from monocytes and smooth
muscle cells derived from endothelium. The intracellular
lipid comprises cholesterol esters, and the extracellular lipid
Atherosclerosis was thought of as a degenerative, progressive
disease, affecting the elderly, and causing symptoms by its
mechanical effects on blood flow, especially in the small
arteries supplying the myocardium and brain. Thus, the
treatment has been surgical for a long time and focused on the
largest and most visible or symptomatic lesions, coupled with a
belief that there was little likelihood of medical management
affecting such an end stage process. Scientific understanding of
atherogenesis is still developing. However, the mechanisms by
which many of the newer variants exert their influence remain
unknown. Recent research into the cellular and molecular
events causing the development and progression of
atherosclerosis, prompted by careful descriptive studies of the
underlying pathology, has shown that atherosclerosis is a
dynamic, inflammatory process that is notably modifiable
Support for this view comes from clinical trials of lipid lowering
agents, especially the “statins”, which have shown minor
effects on the size of existing lesions, but major decrease in
clinical events caused by plaque rupture, causing a beneficial
stabilizing effect on plaque composition. A better
understanding of the molecular and cellular basis of
atherosclerosis will automatically lead to the design of better
diagnostic and therapeutic methods. The aim of this review is
to summarize current understanding of the pathogenesis and
progression of atherosclerosis with risk factors and the leading
causes of it. The review also summarized the newly techniques
and lines of treatment. We didn’t forget to talk about
protective medicine and the recent studies talking about
traditional medicine in the protection of atherosclerosis.
Introduction
,The endothelium maintains vascular tone and blood fluidity
with minimal expression of pro-inflammatory factors under
normal homeostatic conditions. Healthy human arteries
have a tri-laminar structure. The tunica intima is the inner
layer of endothelial cells lining the lumen called the
endothelium. The endothelium is in direct contact with
blood flow and arterial endothelial cells have many highly
regulated mechanisms that are of vital role in maintaining
vascular homeostasis. Despite it is often described as a
monolayer, in human adults it is a more complex and
heterogeneous structure containing some smooth muscle
cells and collagen. It is bound from the outside by internal
elastic lamina, which separates the intima from the tunica
media. The media contains many layers of smooth muscle
cells. In large elastic arteries smooth muscle cells are
arranged in a concentric manner within an extra cellular
matrix rich in elastin which helps store kinetic energy
needed for the transmission of pulsatile flow. The media is
bound on the outside by an external elastic lamina that
separates the media from the adventitia. The adventitia
consists of fibroblasts, mast cells, and a matrix which
contains collagen and proteoglycans. The normal, healthy
endothelium is the major regulator of vascular homeostasis
keeping the balance between vasodilation and
vasoconstriction, inhibition and stimulation of smooth
muscle cell proliferation and migration, and thrombogenesis
and fibrinolysis. The first insight to the importance of the
endothelium in vasomotor modulation started from animal
experiments in the 1980s. It became evident that the
endothelium is an active paracrine, endocrine and autocrine
organ which has the ability to receive various degrees of
stimulation subsequently. a spectrum of endothelial
disturbance exists that depends on the physiological, or
, pathophysiological conditions. Its main vaso regulatory
functions include 1- Secretion of nitric oxide, a strong
vasodilator simply identified as endothelium derived relaxing
factor. Other endothelium-derived vasodilators are
prostacyclin and bradykinin both of which also inhibit
platelet aggregation 2- Secretion of vasoconstrictor
substances such as endothelin and angiotensin II.
Angiotensin II is pro-oxidant, and both stimulate smooth
muscle cell proliferation within the intimal layer. In normal
vascular physiology, nitric oxide is the most important factor
in maintaining the vascular wall in a quiescent state by
inhibiting inflammation, cellular proliferation, and
thrombosis. This is achieved through the expression of some
protective genes (A20, B-cell lymphoma 2 gene) that down-
regulate the expression of transcription factor nuclear factor
since activation of nuclear factor triggers endothelial
activation and makes the endothelium more susceptible to
apoptosis. Nitric oxide limits oxidative phosphorylation in
the mitochondria as well. Laminar shear stress is probably
the major factor that keeps this quiescent, nitric oxide-
dominated, endothelial phenotype with minimal or no
expression of proinflammatory factors.(1)
Early vascular lesions are composed of focal changes
superimposed on the diffusely thickened intima. Grayish
gelatinous lesions are focal areas of excessive fluid build-up
in the intima. Fatty streaks are areas of lipid build-up that
result in insignificant additional thickening of the intimal
layer. The lipids usually have an intracellular localization but
may be partially extracellular. The lipid-laden foam cells are
the macrophages derived from monocytes and smooth
muscle cells derived from endothelium. The intracellular
lipid comprises cholesterol esters, and the extracellular lipid
