Research on Drug Therapy of Atherosclerosis

Yu Cao

1,*,† a

and Xiangrui Chen

2,† b

Southland Christian Schools CA, U.S.A.

Chengdu Foreign Languages School the International Department, Chengdu, Sichuan, China

†

These authors contributed equally

Keywords: Atherosclerosis, PCSK-9 Inhibitors, Marine Omega-3 Fatty Acids, Statin, Bio-Nanomedicines, Berberine.

Abstract: Atherosclerosis is a chronic inflammatory disease in which atherosclerotic plaque accumulated on the walls

of blood vessels and causes narrowing of the arteries. Atherosclerosis usually is asymptomatic in its early

stages, and may causes coronary artery disease, stroke, peripheral artery disease and renal failure in severe

cases. In general, the symptoms associated with atherosclerosis do not appear until after middle age. Most

elderly people who over 65-years-old have atherosclerosis of varying degrees, atherosclerosis is the leading

cause of death and disability in developed countries. The atherosclerotic process is very complex, to

participate in the cells and tissues, including epithelial cells, smooth muscle, monocytes, macrophage,

platelets, lipoprotein, growth hormone, cholesterol, fat and cytokines, etc. Based on these participated

mediators, cells and tissues, scientist developed many drugs to relief atherosclerosis. Prevention of

atherosclerosis generally includes a healthy diet, exercise, quitting smoking, and maintaining a healthy

weight. The drugs include Statins, aspirin, berberine and antiplatelet drugs. In addition to drugs, percutaneous

coronary intervention, coronary bypass surgery can also be used to treat atherosclerosis. Recently, scientists

focused on the “Bio-Nano” which provide more efficient approach to treat atherosclerosis. The advantages of

Nanomedicines are obvious and show its effective function in the clinically experiments, Nanomedicine

possess targeted positing systems and enter capillaries and flow freely in the blood circulation system. The

Nanomedicine with high future expectation worth showing to more people who suffer atherosclerosis. The

review article introduces several distinctive drugs which relief atherosclerosis based on the disease’s

pathogenesis, including their functions, detailed mechanism, how to play its function in human body.

1 INTRODUCTION

According to the global survey, one people has a

stroke among 12 people in China, there are about 2.7

million new cerebrovascular diseases every year, and

trend is increasing year by year, especially in rural

areas (Deright, Jorgensen, & Cabral, 2015). In the

United States, one person has a stroke among forty

people, the ischemic stroke accounts for 87%. The

recurrence rate of ischemic stroke is high, previous

report of Western stroke registries showed that the

cumulative recurrence rate within 5 years after stroke

was 17%-30%. (Carpenter, Ford, & Lee, 2010).

Although ischemic stroke has many etiologies or risk

factors, atherosclerosis is the main pathogenic factor,

especially in people over 5o years of age (Sanne,

Zinkstok, Ludo, & Beenen, et al. 2014).

https://orcid.org/0000-0003-0479-5544

https://orcid.org/0000-0003-0855-6727

Atherosclerosis, driven by the chronic inflammation

of the arteries caused by early endothelial dysfunction

and monocyte recruitment leading to the platelet

aggregation, gradually the plaque was formed with

the accumulation of cholesterol, lipid, or other blood

substance on the blood vessel wall, is the primary

cause of heart disease and stroke (Greenstein, Sun,

Calderon, Kim, Berman. 2000). In fact,

Atherosclerosis took place in people since adolescent

because of the transportation of oxygen and other

material to the rest of body make the arteries thicken

and harder, Healthy arteries are flexible and elastic

(Schreiber, Greenstein, Kim, Calderon, Berman,

1998), but over time, the walls in your arteries can

harden, a condition commonly called hardening of the

arteries. In westernized societies, it is the underlying

cause of about 50% of all deaths (Kim, Kang, Kwon,

440

Cao, Y. and Chen, X.

Research on Drug Therapy of Atherosclerosis.

DOI: 10.5220/0011214500003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 440-447

ISBN: 978-989-758-595-1

2005). To eliminates the patient’s conditions,

researcher developed several efficient drugs to relief

the Atherosclerosis, including statins, which lower

bad cholesterol as low-density lipoproteins, several

drugs such as PCSK-9 inhibition and Marine Omega-

3 Fatty Acids that promoting the cleanness of

cholesterol and the protection for fragile fibrous cap,

antiplatelet drug, and vasodilation drug, which all

researched and developed by the pathogenesis of the

atherosclerosis. These drugs matured during the long

period of applying and studying, But the bio-

Nanomedicine was still in the researching stage and

had profound meaning for atherosclerosis, with high

future expectations. Nowadays, many scientists,

especially Chung Hang Jonathan Choi research

interests include “Bio-Nano '' interactions, and bio-

nanomaterials, drug delivery (Davis, Mark,

Zuckerman, Jonathan, & E, 2010). The Bio-Nano

medicine provided a new perspective for scientists to

study the atherosclerosis, which was a more effective

approaches to help patients relieve. One more

important thing was that atherosclerosis was not a

disease that only affected human’s heart, it also had

subsequent impact on other organs, such as brain,

kidney, liver. Therefore, the information about

medicine that treated atherosclerosis was vital and

necessary for many people who had atherosclerosis or

not. The purpose of the review article was to

summarize different types of medicine and advanced

techniques around the world (Mulder, Jaffer, Fayad,

& Nahrendorf, 2014), because many European

countries, the amount of people who suffer

atherosclerosis increased by a dramatic rate. People

could get more advanced information about these

medicine from the article and know the basic

knowledge about the atherosclerosis, and how to

prevent the formation of atherosclerosis.

1.1 Atherosclerosis

Atherosclerosis is known as Arteriosclerotic Vascular

Disease (ASVD) which is considered an

inflammatory disease of the artery, which can thicken

and harden the arterial wall, and gradually lose

elasticity and narrow lumen in the artery. Injury to

endothelial cells in the artery provokes a series of

inflammatory responses (Nilsson, 2019). The

endothelial cells start to produce cell surface adhesion

molecules like VCAM-1, which can cause monocytes

and T-lymphocytes to adhere to the endothelial cells,

and let endothelial cells move downstream through

squeezing. The endothelial cells also change shape,

and elasticity, which increase the permeability to

fluid, lipids and leukocytes, especially the LDL

(Kang, Martinez, HJ Müller, & E Angléscano. 1997).

When these factors migrate into the intima,

monocytes differentiate into macrophages, which

begin to take up LDL. Macrophages retain the lipid

they take up, and as they become more lipid-laden,

they are referred to as foam cells. Finally, foam cells

will undergo apoptosis and die, but the lipid will

accumulate in the intima (Munro, 1988). That’s why

the fatty streak forms in the artery wall beneath the

endothelium. Over time, the fatty streak can evolve

into atherosclerotic plaques, or they can remain stable

or even regress. Slowly growing plaques expand

gradually due to accumulation of lipid in foam cells

and migration and proliferation of smooth muscle

cells, these slowly growing plaques are matured and

called fibrin caps, which are not prone to rupture. But

other plaque grows more rapidly as a result of more

rapid lipid ruptures, it can trigger an acute thrombosis

by activating platelets and the clotting cascade

(

Cunningham, Gotlieb, 2005).

In detail, atherosclerosis can be divided into three

diseases, including arteriosclerosis of small arteries,

arteriosclerosis in the middle layer and

atherosclerosis. The atherosclerosis appears with the

growth of age, and its rule usually occurs in the

adolescent periods and aggravates and comes on in

the middle and old age. and atherosclerosis is usually

asymptomatic in its early stages, but when it becomes

serious, may cause coronary artery disease, stroke,

peripheral artery disease and renal failure in several

cases (Kutikhin, Brusina, & Yuzhalin, 2013). The

pathogenesis of atherosclerosis is complex and has

not been fully elucidated, the main risk factors are

included hypertension, hyperlipidemia, smoking,

diabetes and genetic factors, the treatment plan for

various risk factors consist of appropriate physical

activity, intervention of lifestyle and food, as well as

drug and surgical treatment. Among them, the drug

therapy is the most effective and quick treatment for

atherosclerosis.

2 DRUG TYPES

Currently there are three kinds of medications that

have been put into use in order to treat atherosclerosis,

which are antiplatelet drugs, anticoagulants, and

cholesterol-lowering drugs.

Research on Drug Therapy of Atherosclerosis

441

2.1 Antiplatelet Drugs

Firstly are the antiplatelet drugs, medicines used to

reduce the aggregation of platelets in the blood

therefore preventing the formation of blood clots.

After the vascular endothelial injury, collagen is

exposed, and stationary platelets, platelet membrane

glycoprotein (GPlb), and von Willebrand factor (vWF)

is influenced, then blood platelets are activated and

show adhesive property. With the effect of platelet

activator, such as ADP, TXA 2, 5-HT and Adr,

platelet membrane receptors GPIIb/IIIa bind to

fibrinogen to form early thrombosis. During the

adhesion, a series of reactions take place, including

the metabolism of arachidonic acid (AA), with

production of TXA2. As the platelets absorb fibrin

network, the blood clot gradually develop into strong

platelet-fibrin mesh.

Aspirin, as one familiar name for a large number

of people, is considered as the most commonly used

oral antiplatelet drug. It works by irreversibly

inhibiting the cyclooxygenase enzyme (COX)

activity in the prostaglandin synthesis pathway

(PGH2). This prostaglandin is a precursor of

thromboxane A2 (TXA2) and PGI2. (Warner,

Nylander, & Whatling, 2011) Also being an epoxide

inhibitor, the inhibition on COX-1 is reversible using

Indobufen. As mentioned, TXA2, a synthetase, is

produced during the activation of platelets, which can

be controlled by a kind of thromboxane synthase

inhibitor called Ozagrel. Another medicine, tirofiban,

works by reversibly combining with platelet receptor

GPIIb/IIIa, preventing receptors and fibrinogen

coming together, therefore resisting platelet

aggregation. Tirofiban is very effective and highly

selective. In antithrombotic therapy, sometimes a

combination of drugs is required as different drugs

taking effects at different stages may be more

efficient.

2.2 Anticoagulants

Anticoagulants play an important role in restricting

clot formation at the injured site. Anticoagulants

mainly focus on thrombin, an important enzyme that

causes the final path of coagulation process, and

coagulation factor X, known as the intersection of

endogenous and exogenous coagulation systems.

They can be divided into thrombin direct (bivalirudin,

argatroban) and indirect (heparin) inhibitors, vitamin

K antagonists and factor Xa inhibitors (rivaroxaban,

apixaban). Direct thrombin inhibitors can inhibit both

fibrin-binding thrombin and free thrombin, while

indirect thrombin inhibitors can only work on free

thrombin. Xa factor, a kind of vitamin K - dependent

serine protease, is the speed-limiting factor in the

formation of thrombin. The inhibitors have a strong

inhibitory effect on both Xa factors and

prothrombinase complex. As the role of factor Xa

infers, the inhibition on factor Xa is thought to be

more effective than the effect of thrombin inhibitors.

(Viladrich, E Daudén Tello, Solano-López, FJ López

Longo, Samso, & P Sánchez Martínez, et al. 2016)

2.3 Cholesterol-lowering Drugs

There are also cholesterol-lowering medicines, which

are used to lower lipid level in the blood, particularly

the low density lipid (LDL) cholesterol. Statins is one

of the cholesterol-lowering medicines ， including

simvastatin, atorvastatin, and pravastatin. Bile acid

sequestrants—colesevelam, cholestyramine and

colestipol—and nicotinic acid are other types of

medicine that may be used to reduce cholesterol

levels.

Among those, the statins are the first choice of

lipid-lowering drugs. HMG-CoA reductase is a rate-

limiting enzyme in the cholesterol synthase system.

By inhibiting it, statins can reduce cholesterol

synthesis, reduce cholesterol concentration in plasma

and tissue cells, promote the activity of

concentration-dependent LDL receptors, and

accelerate the catabolism of LDL. It can also reduce

the synthesis of very low density lipoprotein, which

is VLDL, and convert VLDL into LDL reduction.

Therefore, it is proven that statins can significantly

decrease TC and LDL levels, reducing TC levels by

30%-40% and LDL-C levels by 35%-45%.

3 PROVE TO CLEAR

SUBSTANCE

3.1 PCSK9 Inhibitor

Proprotein convertase subtilisin/kexin type-9 (PCSK-

9) is a key player in plasma cholesterol metabolism

that can bind to LDL-R at the liver and stimulates the

absorption and degradation of these receptors,

eventually lowering the receptors levels (Cameron,

Ranheim, Kulseth, Leren, & Berge, 2008). PCSK-9 is

a 72-kd protease, expressed highly in the liver with

three recognizable domains, an N-terminal pro

domain, a catalytic domain, and a carboxyl-terminal

domain of unknown function, and these can bind to

the LDL receptor on the surface of cells, when the

nuclear environment reach the acidic level, the

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

442

affinity of PCSK-9 for the LDL receptor increases by

nearly 150-fold, and PCSK-9 binds to the epidermal

growth factor (EPG) repeat A of the LDL receptor,

which known as a crucial for recycling of the LDL

receptor from endosome to the cell surface (Mabus,

Palmer, Prouty, Hornby, & Wade, 2010). Overall,

PCSK-9 disrupts the route of the LDL receptor,

making it miss the way to reach the cell surface.

So, the drug called PCSK-9 inhibitors can play its

function through inhibition of PCSK-9, the

degradation of LDL-R is prevented thereby

improving the absorption by the liver of LDL

cholesterol particles, which consequently leads to

lower LDL cholesterol plasma concentration (Norata,

Garlaschelli, Grigore, Raselli, Tramontana, &

Meneghetti, et al. 2010). For now, the PCSK-9

therapy is suitable in a wide range of patients

provided that they express LDL-R.

3.2 Marine Omega-3 Fatty Acids

Marine Omega-3 Fatty Acids are nutrients people get

from food or supplements that help build and

maintain a healthy body. They’re key to the structure

of every cell wall people have, also an energy source

and help keep heart, lungs, blood vessels and immune

system working the way they should. Based on the

function of Marine Omega-3 Fatty Acids, researcher

found the potentially possibility to relief

Atherosclerosis (Calder, 2012). Marine Omega-3

Fatty Acids can make the fibrous cap or plaque

become more stable, the patients who ingest Marine

Omega-3 Fatty Acids in a long time, the plaque from

patients are more likely to be type IV, which possess

well-formed necrotic core with an overlapping thick

fibrous cap, IV plaque can be considered a good

fibrous cap (Kühnast, van der Hoorn, JoséVan,

Havekes, Liau, & Jukema, et al. 2012). Marine

Omega-3 Fatty Acid also lowers the level of these

immune cells surrounding the plaque. Rupture of

plaque is an extremely acute occurrence that exposes

the plaque contents to the high prothrombotic

environment of the vessel lumen, which can lead to

myocardial infarction, stroke or another vascular

event. Also, inflammatory cells, including

macrophages, T cells, mast cells, are typically

abundant at such locations within thin and tender

fibrous cap that easier to rupture, and these cells can

produce a range of medicator and enzymes that can

thin and weaken the fibrous cap making the plaque

vulnerable and unstable (Eschen, Christensen, Toft,

& Schmidt, 2005). So essentially Atherosclerosis is

an inflammatory event called plaque that can rupture

and lead to a series of dangerous consequences.

Marine Omega-3 Fatty Acids can stabilize

atherosclerotic plaque by decreasing infiltration of

inflammation and immune cells, like

monocyte/macrophages and lymphocytes, into the

plaques or by decreasing the activity of these cells

once in the plaque to lower the possibility of rupture

of plaque. There are two crucial ones- EPA and DHA

which are primarily found in certain fish, ALA

(Alpha-Linolenic Acid), another Omega-3 Fatty

Acids, is found in plant sources such as nuts and seeds

(Calder, 2012). EPA and DHA give rise to resolving

which are anti-inflammatory and inflammation

resolving, and also affect production of peptide

mediators of inflammation.

Figure 1: Vasodilatory response to reactive hyperemia after

omega-3 or placebo treatment. Pair-wise compared curves

using global fitting are shown (p = 0.01). Data points

represent mean ± SD. (Dangardt, Osika, Chen, & et al.

2010).

4 NEWTYPE DRUGS

4.1 Target Medications

Several nanomedicines are exemplified by the US

Food and Drug Administration’s approval for various

conditions. The main idea about nanomedicine is

about targeting specific substances in the blood, like

nonspecific targeting, specific targeting of the

vasculature, etc. Nanoparticle-facilitated therapeutics

can potentially be applied to target the liver and

change lipid levels systemically, or they can directly

inject the high density of lipoprotein nanoparticles to

enhance the transport of cholesterol in plaque to the

liver for excretion. And nanomedicine can deplete the

recruitment of monocytes or decrease plaque

inflammation and neovascularization (Tian, Lu,

Feng, & Melancon, 2018). Nanomedicine is a new

type and still developing medication.

Nanomedicine’s delivery systems can solubilize

drugs, improve drug half-life, improve drug

distribution in vivo and reduce toxic and side effects.

Research on Drug Therapy of Atherosclerosis

443

Bio-Nanomaterials is considered as a new strategy to

curing Atherosclerosis and the application of the

strategy to promote the specific delivery of

therapeutic molecules to atherosclerotic plaques is

under active investigation. A classic example is the

doxorubicin-containing liposome, the first Bio-

Nanomedicine approved by the United States Food

and Drug Administration for treating cancer in 1995

(Maranh, Tavares, AF Padoveze, Valduga, Oliveira,

& Rodrigues, 2006). Because Bio-Nanomedicine

contains partially or completely of biomolecules,

such as lipids, sugars and nucleic acid and proteins,

which is easier to control or develop the methods to

change the dimensional structure or the number of

biomolecules. An efficient approach to apply bio-

nanomedicine is to let the drug be injected into a lipid

which acts as a vector, and the drug-encapsulated

lipid could target the atherosclerotic plaques. In 2016,

Scientists (Kim, Rutka, & Chan, 2010) loaded

carmustine, a lipophilic chemotherapeutic, into lipid

NPs for targeting atherosclerosis plaques. They set a

series of experiments which inject the bio-

Nanomedicine into the atherosclerotic New Zealand

rabbits, and the drug-encapsulated NPs can reduce the

plaque size. But the method still was in the

experiment stage. Actually, all Bio-Nanomedicine

was applied based on the pathogenesis of

Atherosclerosis. The migration and death of

monocyte and macrophage can destroy local tissue of

architecture by secreting proteases and inflicting

oxidative stress on the vessel wall. And some

enzymes would digest the fibrous cap, thereby

initiating plaque rupture. So, the macrophage was

readily ingested nanomaterial and could be the prime

of target for novel therapeutics. Lobato et al.

(Lobatto, Fayad, Silvera, Vucic, Calcagno, & Mani,

et al. 2010) develop the methods of using bio-

nanomedicine to inhibit plaque macrophage

inflammation directly, they observed marked and

persistent plaque inflammation inhibition using a

liposomal nanoparticle containing glucocorticoids in

the atherosclerotic mouse.

One new study of Bio-Nanomedicine is using a

“camouflage” to inhibit the atherosclerotic plaque.

Because when strangers enter into the bloodstream in

a human's body, the immune system would start to

attack the drug and make it fail (Yamawaki, & Iwai,

2006). The methods used the methods that cover the

drug with the common cell membrane that the

immune system recognized and familied, and then

inject it into blood, the immune system still would

attack the drug but less than without the

“camouflage”. The Biomimetics nanometer therapy

(Rienzo, Jacchetti, F Cardarelli, Bizzarri, F Beltram,

& Cecchini, 2013) in the study is to read cell

membrane packages on the surface of nanodrugs,

implementation of nanodrugs “camouflage”, which

can effectively reduce the possibility that the body

system removes the nanodrugs, so that nanodrugs can

make long-term-nanodrug efficiency in the blood

circulation, thereby promoting nanodrugs targeting to

the pathological changes of atherosclerosis.

4.2 Berberine as an Antiatherosclerosis

Drug

Scientists have been also working on new type drugs

for higher effectiveness as atherosclerosis is still a

serious disease today. One of the existing drugs that

mainly works on digestive system has been found to

behave as a lipid-lowering drug. Berberine, which a

lot of studies have been done on, has antibacterial

effect on hemolytic streptococcus, Staphylococcus

aureus, Neisseria gonorrhoeae and Shigella dysentery,

etc., and can enhance leukocytophagocytosis. It has

varying degrees of inhibitory effect on tuberculosis

bacillus and yersinia pestis, and also has inhibitory

effect on amoeba in rats. With the strong support of

the National Natural Science Foundation of China,

the research team led by Dr. Jiang Jiandong, director

of the Institute of Medical Biotechnology of the

Chinese Academy of Medical Sciences, has made

breakthroughs in gene sequence, cell, animal

experiments and clinical treatment. The

pharmacodynamics, pharmacodynamics and

molecular mechanism of berberine in reducing blood

cholesterol and triglyceride were systematically

studied. They found that berberine lowers blood

lipids at the post-transcriptional level by acting on

mRNA (messenger RNA) that stabilizes LDL

receptors in the 3'UTR region, a mechanism

completely different from that of statins currently

used to reduce blood lipids. This provides a new

molecular target for finding new hypolipidemic drugs

in theory. Clinical studies have shown that oral

berberine (1 gram per day for 3 months) can reduce

cholesterol, low density lipoprotein and triglyceride

by 20% ~ 35% in patients with hyperlipidemia, which

has been further confirmed by hyperlipidemia golden

hamster model animal experiments. Dr. Jing Wei

from Nanjing First Hospital and Dr. Jingwen Liu

from Veterans Hospital paralto, California, USA,

both indicated that berberine may be a substitute for

statins, and is expected to be used in combination

with statins in the treatment of cardiovascular

diseases.

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444

4.2.1 BBR Protect the Cardiac Muscles by

Raising the Concentration of Protein

Kinase of Ischemic Myocardia

The activated adenosine 5’-monophosphate-activated

protein kinase (AMPK), as the key particles in the

regulation of biological energy metabolism, can

restrain the consuming of adenosine triphosphate

(ATP). On the other hand, it can stimulate cells to

produce more ATP, therefore prolonging ATP supply

time within the cells, which plays a protective effect

to ischemic cardiac muscle cells.

Calcium ions are vital to the human body, because

they participate in the clotting process, muscle

contractions, neurotransmitter synthesis and release,

hormone synthesis and secretion, plus they are the

important elements in bone formation. When BBR

reduces the number of alpha-adrenergic receptors on

the membranes of the cardiac muscles, calcium influx

is inhibited, and cell apoptosis is blocked in order to

protect myocardial cells. (Cheng-Yi, H. U., & Zhi-

Xian, M. O)

4.2.2 Trials of Patients with Related

Diseases

According to a series of trials involving 874 patients

who had type 2 diabetes, hyperlipidemia,

hypercholesterolemia and related diseases. Ten

experiments were single-center experiments, and one

study was multi-center experiments. Patients with

type 2 diabetes were included in four studies. One

study recruited hyperlipidemia patients with type 2

diabetes. And there was a study of patients with

impaired glucose tolerance and hyperlipidemia.

Patients with hyperlipidemia were included in two

other studies. And another two studies included

patients with hypercholesterolemia. Besides, one of

the research projects included recruited patients with

polycystic ovary syndrome and insulin resistance.

Six studies randomly assigned participants to take

berberine under lifestyle changes and without

changes, and placebo with or without intervention.

According to experiment description, two trials

showed combined effects of berberine and oral

hypoglycemic agent with a controlled hypoglycemic

agent. Two others compared the combination action

of berberine and simvastatin with a simvastatin

control. One trial compared a combined intervention

of berberine and cyproterone acetate with placebo

plus cyproterone acetate. Two berberine preparations

were used in the inclusion trials, berberine chloride

tablets (used in 10 trials) and berberine chloride

liposome capsules (used in only 1 trial). Different

doses of berberine were used in these trials. The

intake of berberine is generally between 0.5-1.5 g per

day. Daily intake of berberine is divided into two or

three doses. The dose of berberine did not change

during the 8 trial periods. Three trials reduced the

dose of berberine when gastrointestinal discomfort

occurred during the study period.

A comprehensive estimate of the effect of

treatment on lipid concentration is summarized in

Figure 3. There was significant statistical

heterogeneity in blood TC and TG results among

different studies (P <0.10). The results showed that

there was significant difference between the

berberine treatment group and the control group.

Berberine was significantly better than the control

group in improving blood TC (P < 0.00001;Md-0.61

easier/L;95% CI-0.83 ~ 0.39) and TG (P

<0.00001;Md-0.50 mmol/L: 95% CI-0.69 ~

0.31).There were no statistically significant

differences in LDL-C and HDL-C among tests (P >

0.10).Compared with the control group, the level of

LDL-C was significantly increased in patients taking

berberine (P <0.00001; Md-0.65 easier/L; 95% CI -

0.76 -- 0.54) and HDL-C (P =0.001;MD 0.05 easier/L;

95% CI 0.02 to 0.09).( Dong, H., Zhao, Y., Zhao, L.,

& Lu, F.. (2013)

Figure 2: Meta-analyse of the effects of berberine on total

cholesterol levels.

5 CONCLUSIONS

In conclusion, atherosclerosis is a chronic vascular

disease that usually occurs in the aorta and muscular

arteries, such as the coronary, cerebral, renal, and

carotid arteries (Stary, Blankenhorn, Chandler,

Glagov, Insull, & Richardson, et al. 1992). These

disease with high death rate were caused by

atherosclerosis, so the medication for reliving

atherosclerosis was more vital. Clinically, there are

many drugs used for the pathogenesis of

atherosclerosis, such as dyslipidemia and

hypertension, and their action pathways and targets

Research on Drug Therapy of Atherosclerosis

445

are different. Based on the dyslipidemia, which was a

basic pathogenesis of atherosclerosis, scientists

developed the drug called PCSK-9 inhibitor, which

inhibits the PCSK-9 that prevents the LDL receptor

bind with cholesterol. And statin was the most

common drug that was used in relieving

atherosclerosis, statin could lower cholesterol level,

its working process to block a specific substance that

participated in process making cholesterol. Drugs,

like statin, PCSK-9 inhibitor, antiplatelet medication,

were tested and already used for a long time (Taleb,

Witztum, & Tsimikas, 2011). They possessed high

stability and took advantage in the drug market. In

addition, different drugs can be used in combination

according to different mechanisms of action to

achieve better efficacy. Nowadays, some kinds of

bio-nanomedicine are undergoing development. They

achieve progress in the experimental stage, which

motivates people to study further and persist.

Scientists indicated the bio-Nanomedicine with

“camouflage” might potentially become the most

expectable drug (Stenosis, 1995), which reduces the

rejection phenomenon. Within the potentiality of bio-

nanomedicine, it would become the mainstream of

atherosclerosis, it is more precise and readily but still

undergoes experiment clinically. In the future, Bio-

nanomedicine may would be the mainstream to cure

or treat some diseases, which could provide more

efficient treatment for patients and more precise to

target its pathological position. Scientists might

should pay more attention on the accuracy of target

with the bio-nanomedicine and how to use magnetic

field to kill cancer cells.

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