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Exercise for Prevention and Relief of Cardiovascular Disease:
Prognoses, Mechanisms, and Approaches
and Jinqi Meng
Department of Physiology, Hebei Medical University, Shijiazhuang, China
Department of Sports, Hebei Medical University, Shijiazhuang, China
Correspondence should be addressed to Jinqi Meng; firstname.lastname@example.org
Received 10 December 2018; Revised 1 February 2019; Accepted 19 March 2019; Published 9 April 2019
Guest Editor: Fiammetta Monacelli
Copyright © 2019 Danyang Tian and Jinqi Meng. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work
is properly cited.
This review is aimed at summarizing the new ﬁndings about the multiple beneﬁts of exercise on cardiovascular disease (CVD). We
pay attention to the prevalence and risk factors of CVD and mechanisms and recommendations of physical activity. Physical
activity can improve insulin sensitivity, alleviate plasma dyslipidemia, normalize elevated blood pressure, decrease blood
viscosity, promote endothelial nitric oxide production, and improve leptin sensitivity to protect the heart and vessels. Besides,
the protective role of exercise on the body involves not only animal models in the laboratory but also clinical studies which is
demonstrated by WHO recommendations. The general exercise intensity for humans recommended by the American Heart
Association to prevent CVD is moderate exercise of 30 minutes, 5 times a week. However, even the easiest activity is better than
nothing. What is more, owing to the diﬀerent physical ﬁtness of individuals, a standard exercise training cannot provide the
exact treatment for everyone. So personalization of exercise will be an irresistible trend and bring more beneﬁcial eﬀects with
less ineﬃcient physical activities. This paper reviews the beneﬁts of exercise contributing to the body especially in CVD through
the recent mechanism studies.
1. Cardiovascular Diseases: Prevalence and
CVD is a class of diseases which are related to the heart or
blood vessels including stroke, heart failure, hypertension,
coronary artery diseases, heart arrhythmia, peripheral artery
disease, and atherosclerosis . Individuals with CVD are
found to have the accompanying raised blood pressure, ele-
vated glucose, smoking, obesity, lack of exercise, excessive
alcohol consumption, and dyslipidemia. Fortunately, CVD
can be properly managed and prevented by controlling blood
pressure, glucose, lipid, smoking, and alcohol drinking and
through lifestyle modiﬁcations for sleep, emotion, exercise,
and diet, which are called SEED intervention . With the
aging of population in the world, CVD has become the
leading cause of death globally. Approximately 17.9 mil-
lion deaths in 2015 were caused by CVD in the world
. The percentage of Chinese older than 60 has increased
to 16% in 2015 which directly leads to a consequence that
cardiovascular disease is becoming the leading cause of
death in China . Multiple risk factors contributing to
CVD include obesity, high blood pressure, diabetes, aging,
male sex, metabolic syndrome, and physical inactivity.
Determined by body mass index (BMI), obesity refers to
the condition of those who have over 30 BMI and overweight
includes persons with BMI more than 25. The prevalence
among people of obesity has exceeded 50% in most countries
and is increasing in both adults and children over the past
few decades worldwide . Obesity is found to increase
blood volume, CRP, and TNFαwhich cause cardiac remodel-
ing and inﬂammation. Obesity also aggravates the risks of
high blood pressure, stroke, myocardial infarction (MI),
and insulin resistance, which are all risk factors of CVD .
Furthermore, mortality and morbidity of CVD have been
shown increasing in overweight populations, especially in
those with abdominal obesity .
As the most common form of diabetes, type 2 diabetes is
a chronic metabolic disease which is characterized by high
Oxidative Medicine and Cellular Longevity
Volume 2019, Article ID 3756750, 11 pages
blood glucose, low insulin sensitivity. With the incidence of
diabetes continuing to rise, the number of patients diagnosed
with diabetes has swelled from 30 million in 1985 to 382 mil-
lion in 2014, and scientists predict 592 million people will
have diabetes by 2035, almost 1 in 10 persons suﬀering from
this disease . Besides aﬀecting aging people, this disease
also inﬂuences an increasing number of young populations
and even children . Lots of evidences and studies demon-
strate that type 2 diabetes acts as an independent risk factor
for CVD. The patients who are diagnosed with type 2 diabe-
tes have a worse prognosis and therapeutic eﬀects of CVD
compared with those without diabetes. CVD death rates with
diabetes in the United States adults are 1.7 times higher than
those without diabetes . The huge medical care burden of
type 2 diabetes generally attributes to vascular complications
like MI, hypertension, peripheral vascular disease, and
coronary artery disease .
Aging is a gradual, systematic, irreversible, degenerative
process in the body, which results in weakness, disease, and
even death. As there is an average increasing lifespan for
humans, there will be approximately 20% of the population
over 65 by 2030. Aging is an inevitable and important deter-
minant for CVD which leads to the decline of mitochondrial
functions, excess reactive oxygen species (ROS) production,
and disorder of Ca
levels . Aging is relevant to the
progressive damage in various physiological processes and
increases incidence of atherosclerosis, hypertension, and
stroke , thus inducing an elevating risk of cardiac and
arterial systematic disorders. Studies show parts of the key
genes regulating lifespan including AMPK, m-TOR, and
IGF-1; sirtuins are closely related to CVD progress .
Epidemiologists demonstrate the diﬀerent CVD occur-
rence rates between males and females. Clinical studies show
that the onset of heart attack is delayed 9 years in women
compared with men . In a cross-sectional survey on
hospitalized patients with coronary artery disease, women
were found 3.1 years older than men . It is widely
believed that estrogen is the prominent protective element
for females . Besides, women tend to have a better aware-
ness of weight measurement and their waist circumference if
they have central obesity, which would lower the risk of
adiposity and dyslipidemia. Smoking and alcohol drinking
are severe risk factors for CVD, which are more common
lifestyle behaviors in men compared to women .
Metabolic syndrome is a condition characterized by low
high-density lipoprotein (HDL), high triglycerides (TG),
high blood pressure, high blood glucose, and central obesity,
associating with the risks of developing to CVD and type 2
diabetes. Studies show that metabolic syndrome aﬀects
30-40% of people older than 65 by doubling the risk of
getting CVD . Low HDL and high TG are associated with
elevated levels of low-density lipoprotein (LDL), which
increase the risk of having atherosclerosis . High glucose
links to dysfunctions of glucose uptake and catabolism and
induces high oxidative stress, dysfunction of endothelial cells.
High blood pressure leads to cardiac and vascular injury.
Central obesity is related to maldistribution of free fatty
acid, overproduction of inﬂammatory molecules, and leptin
Physical inactivity has been identiﬁed as the fourth risk
factor of death worldwide, leading to approximately 3.2
million deaths annually. Various studies show an obvious
dose-response relationship between increased physical activ-
ity and decreased occurrence rate of CVD including reduced
blood pressure, body weight, ox-LDL, and elevated glucose
tolerance. A systematic review estimates that the lack of
exercise leads to 6% of coronary heart disease occurrence
worldwide. Deﬁciency in physical activity leads to obesity,
increasing endogenous inﬂammatory molecules and coagula-
tion factors. In addition, there is coordinated protective
eﬀects to decrease the overall risk of incident CVD by exer-
cise [22, 23]. So having a healthy diet, avoiding smoking,
and keeping regular physical activity are the three pieces of
advice the WHO recommend to avoid CVD.
2. Mechanisms of Action for Physical Exercise
Many considerable evidences support the therapeutic and
protective eﬀects of exercise on the body, including improve-
ment of insulin sensitivity of diabetic mice, attenuating sym-
pathetic activity, arterial pressure, and heart rate in the
spontaneously hypertensive rats . Mitochondrial bio-
genic response, components of the electron transport chain,
mtDNA, and related lipid metabolic pathways are all
increased after exercise training . Here, we talk about
the beneﬁts of exercise on cardiovascular disease from the
2.1. Insulin Sensitivity and Blood Glucose Control. Type 2
diabetes mellitus is a kind of chronic disease characterized
by obesity, hyperglycemia, impaired insulin secretion, and
insulin resistance . Studies show that diabetic rats with
exercise training present reduced body weight, decreased
TG levels, and diminished blood glucose levels compared
with those sedentary rats [27, 28]. PPARγknown as
“energy-balanced receptor,”is well studied in metabolic dis-
orders. Carnitine palmitoyl transferase-1 (CPT-1) mainly
transports fatty acids into mitochondria for medium-chain
acyl-CoA dehydrogenase (MCAD) catalyzing β-oxidation.
Through upregulating PPARγand its target genes, CPT-1
and MCAD, exercise alleviates hepatic steatosis, promotes
glucose uptake, and improves insulin sensitivity in nonalco-
holic fatty liver disease mice . Exercise stimulates the
translocation of glucose transporter type 4 (GLUT4) from
the cytoplasm to the cell membrane, thus promoting glucose
uptake and improving insulin resistance . Besides,
improved insulin sensitivity is independent with exercise
modality. High or low intensity of exercise and aerobic or
anaerobic training lead to improvement in glucose clearance
curve and insulin sensitivity .
Besides improving insulin sensitivity, exercise facilitates
glucose uptake and usage via insulin-independent mecha-
nisms. Once glucose enters muscular and adipose cells, it will
be phosphorylated by hexokinase which is an irreversible
catalytic reaction to form glucose 6-phosphate (G-6-P) that
cannot diﬀuse back out of cells. Glycolysis and glycogenesis
started from G-6-P and promote glucose uptake by cells
and usage in cells to aﬀect blood glucose. Exercise increases
2 Oxidative Medicine and Cellular Longevity
G-6-P level in the skeletal muscles accompanying increased
GLUT4, hexokinase level, and glycogen synthase activity,
which ﬁnally improve glucose tolerance and decrease blood
glucose level .
2.2. Lipid Proﬁle. Cholesterol is a soft waxy fat that our body
needs to function well. But too much cholesterol will become
risk factors for human diseases like heart disease, stroke, and
atherosclerosis . For those who have been diagnosed with
diabetes, heart disease, and stroke or people who are taking
medicine to control cholesterol level, taking cholesterol test
every year is necessary . Generally, a cholesterol test
includes total cholesterol, LDL, HDL, and TG . Standard
management strategies like drug therapy and diet control are
generally used to lower serum cholesterol to prevent heart
disease. However, some people are insensitive to statins or
cannot tolerate statins. Hence, other ways need to replace
or be used together with statins. More and more evidences
support aerobic exercise as a positive method for alleviating
plasma dyslipidemia and improving the prognosis of cardio-
vascular diseases . Through using meta-analyses to inves-
tigate exercise and lipid proﬁles, Pedersen et al. concluded
that exercise led to beneﬁts of physical health . A pro-
spective cohort study lasting for 10 years about exercise and
lipid metabolism shows that the risk of mortality is signiﬁ-
cantly reduced by combining statins with exercise, especially
compared to other therapy alone . Comparing with LDL
and TG, HDL is more sensitive to exercise. Studies indicate
that HDL is increasing more or less both in humans and rats
after exercise [39, 40]. For the “bad”cholesterol LDL, the
eﬀects of exercise reduce the serum levels signiﬁcantly in rats
. However, the eﬀects are not consistent in humans,
which may be due to the diﬀerent dietary habits and living
conditions [41, 42]. It is strongly accepted and reported that
exercise leads a high requirement of energy which induces
decreasing of plasma TG concentrations .
2.3. Blood Pressure. Blood pressure is elicited by the force
exerted by the blood against the blood vessels, which depends
on the ejection of the heart and resistance of the blood ves-
sels. Hypertension is another name of high blood pressure,
a disease related to heart attack, stroke, heart failure, and
other problems . Exercise always leads to a postexercise
hypotension, and both normotensive and hypertensive
persons experience a transient reduction in blood pressure.
The reduced magnitude may achieve the point wherein
patients with hypertension recover to the normal blood pres-
sure levels. In a meta-analysis, they investigated the eﬀects of
acute exercise on blood pressure response. There were signif-
icant changes, reduction of 4.8 mmHg for systolic blood pres-
sure (SBP) and 3.2 mmHg for diastolic blood pressure (DBP).
The epidemiological study demonstrates that 2 mmHg
decline in SBP leads to 6% reduction of stroke mortality
and 4% reduction of coronary heart disease mortality, and a
decrease of 5 mmHg causes the reduction of mortality of
these diseases by 14% and 9%, respectively . So the
meta-analysis results conﬁrm the undoubted place of nonin-
vasive therapy method, acute exercise.
The transient reduction only lasts for a few hours and
would recover after rest. However, the beneﬁts of physical
activity cannot be ignored because of chronic treatment of
exercise showing signiﬁcant changes among subjects. The
vasodilator activity leads to the decrease of blood pressure.
On the contrary, increased blood pressure is caused by
vasoconstriction. Moderate-intensity exercise causes a vaso-
dilatory response and decreases the vasoconstricting response
and lipid in rat aortas, which exhibits a decrease in diastolic
blood pressure [46, 47]. In addition to the vascular tone, exer-
cise decreases blood pressure through lowering oxidative
stress and inﬂammation levels. In the spontaneous hyperten-
sion rats (SHR), exercise normalizes the increased collagen
deposition and diminished fenestra size in the internal elastic
lamina, meaning that exercise shows the beneﬁt roles in
normalizing the increased vascular stiﬀness and decreased
vascular distensibility in both small mesenteric arteries and
coronary arteries . However, high-intensity exercise leads
to the opposite eﬀects that increased oxidative stress, elevated
blood pressure, and high vasoconstrictor activity are found
. Some studies report that males tend to achieve greater
reductions than females from the exercise training . How-
ever, the authors ignore the factors of menstrual cycle in the
female subjects which aﬀect the regulation of the autonomic
nervous system . Studying the eﬀects of exercise on circa-
dian rhythms using ambulatory blood pressure monitoring,
there are signiﬁcant reductions of daytime BP, but no obvious
changes are observed at nighttime BP .
2.4. Blood Viscosity, Platelet Aggregation, and Thrombosis
Proﬁle. Blood viscosity in normal conditions is like a Newto-
nian ﬂuid which is inﬂuenced by hematocrit, shear rate of
blood ﬂow, vascular caliber, and temperature. Elevated blood
viscosity which is associated with blood resistance increases
risks of cardiovascular complications. Blood viscosity is
decreasing during exercise accompanied by decreased sys-
temic vascular resistance . More nitric oxide (NO) is
produced attributed to greater shear stress in exercise and
promote vasodilation [53, 54]. During exercise, erythrocyte
volume is slightly increased; however, a much higher increase
of plasma volume is generated which ﬁnally results in
lower blood viscosity. Decline in plasma ﬁbrinogen level
is observed under the eﬀect of exercise which plays important
roles in declining erythrocyte aggregation and decreasing
blood viscosity .
Platelet is a small volume component in blood which has
no cell nucleus generated from megakaryocytes. Through
forming thrombus, the platelets exert primary function of
maintaining hemostasis of blood ﬂow. Once an injury occurs,
the platelets in the circulation will be activated and aggre-
gated to the interrupted endothelial site to plug the hole
. So abnormality in platelet activation leads to a variety
of atherosclerotic diseases mainly through excess thrombosis
in small arteries like coronary arteries and blood vessels of
the brain . Exercise training presents an antithrombotic
manner through platelet functional regulation. Through
enhancing blood ﬂow, exercise enhances endothelial NO
production which counteracts platelet activation . The
moderate physical activity decreases both platelet adhesion
3Oxidative Medicine and Cellular Longevity
and aggregation through downregulating intracellular cal-
cium levels and increasing cGMP levels . It is recom-
mended by government guidelines that physical activity is
an eﬀective way to prevent thrombosis . Exercise is also
used to improve chronic complications of deep venous
thrombosis, postthrombotic syndrome. A six-month exercise
training markedly increases leg strength, hamstring and
gastrocnemius ﬂexibility, and overall ﬁtness . However,
studies showed that the strenuous short-term exercise acti-
vated platelets and promoted aggregation of platelets, thus
increasing the risk of MI or cardiac arrest. This suggests that
acute exhausting exercise may trigger clot formation, but the
mechanisms remain to be clariﬁed .
2.5. Endothelial NO Production. NO is a gaseous signaling
molecule playing an irreplaceable role in a variety of biolog-
ical processes. It is catalyzed by various nitric oxide synthase
(NOS) enzymes by using substrate L-arginine. Known as an
endothelial-derived relaxing factor, NO contributes to not
only endothelial-dependent relaxation (EDR) but also to
the maintenance of endothelial function . The endothe-
lium is a single layer of cells in the intima of vessels separat-
ing blood from the tissue. The functions of the endothelium
involve regulating angiogenesis, balancing vasoconstriction
and vasodilation, adjusting smooth muscle cell proliferation,
and excreting endocrine. The intact endothelium acts an
indispensable role in vessel homeostasis . In a cross-
sectional study with 184 healthy individuals, L-arginine was
reduced and production of NO was increased after exercise
training . The mechanisms may be partial that exercise
training leads to increased blood ﬂow and shear stress, con-
tributing to endothelial NOS (eNOS) expression, NO release,
and artery relaxation. NO activates soluble guanylate cyclase
which increases cGMP and therefore activates protein kinase
G (PKG). In blood vessels, PKG activation always induces
relaxation and regulates blood pressure. In the heart, PKG
works as a brake on stress response signaling . Through
increasing vascular AMPK/PPARδ, exercise suppresses
endoplasmic reticulum stress, thus increasing endothelial
NO bioavailability. Exercise shows preserved EDR in the
aorta and mesenteric artery in high-fat diet rats and db/db
mice . In the aging-induced downregulation of VEGF
signaling cascade in the heart, exercise upregulates VEGF,
its receptors Flt-1 and Flk-1, and the downstream signaling
pathway Akt/eNOS . Increased NO production usually
facilitates angiogenesis and vascular permeability.
Dysfunction of EDR and decrease of cGMP in both
plasma and vascular tissue are found in diabetic rats. How-
ever, chronic exercise improves endothelial function through
releasing NO in the aorta. Interestingly, exercise does not
aﬀect the vascular function in normal rats administrated with
L-arginine but improves vascular function in the aortas from
diabetic rats . In the high fat-induced obese mice,
impaired EDR, reduced NO bioavailability, and decreased
phosphorylation of eNOS are found in the coronary arteries
which can be normalized by exercise. Through injecting
β-adrenoceptor agonists, isoproterenol for 8 days, Yang
recapitulated cardiac hypertrophy which was regarded as
the primary risk factor for heart failure. After 4 weeks of
exercise training, the eNOS expression did not change, but
the phosphorylation of serine residue 1177 with an activating
impact on eNOS was increased and the phosphorylation at
threonine residue 495 with an inhibitory impact on eNOS
was decreased. As a result, exercise promoted NO production
and attenuated cardiac remodeling, echocardiographic and
hemodynamic changes after β-adrenergic overload .
2.6. Leptin Sensitivity. Leptin is a 16 kDa circulating hormone
which is predominantly released by adipocytes to exert
regulation of food intake and energy metabolism. Through
binding to leptin receptors on hypothalamic cells, leptin
inhibits hunger, prevents weight gain, and promotes positive
energy balance . So leptin deﬁciency or leptin resistance
promote diabetes, obesity, and other metabolic disorders.
Exercise improves leptin resistance and sensitivity, attenuates
body weight, and promotes homeostatic control of energy
balance through inﬂuencing the leptin receptor in the ventro-
medial hypothalamic nucleus of obese mice [71, 72]. It also
directly works on leptin receptors to induce NO-dependent
vasodilation expressed in endothelial cells . A decreased
leptin sensitivity and hyperleptinaemia are found in obese
mice coronary arteries, demonstrating leptin resistance and
low leptin sensitivity. Exercise maintains leptin sensitivity
of obese mice and preserves leptin receptor, thus exerting
endothelial protection . Exercise facilitates SOCS3
expression and improves leptin resistance in the liver and
muscle of high-fat diet-induced rats . Leptin sensitivity
is restored by exercise manifested as facilitating fatty acid
toward oxidation and away from triacylglycerol stores .
Through activating leptin, exercise also initiates the down-
stream JAK/STAT signal transduction pathway in obese mice
to protect against myocardial ischemia-reperfusion injury
. Shapiro et al. found that leptin overexpression failed
to reduce body weight in obese rats, and chronic leptin treat-
ment aggravated the diet-induced obesity. Besides, wheel
running for obese rats was insuﬃcient to lower body weight.
However, combinational administration of exercise and
exogenous leptin dramatically induced weight loss and
improved leptin sensitivity . That means exercise may
directly activate leptin signaling pathway or improve leptin
sensitivity via coordinating with other therapeutic methods.
2.7. Modulation of Autonomic Function. The autonomic
nervous system, regulated by the hypothalamus, consists of
sympathetic nervous system, parasympathetic nervous sys-
tem, and enteric nervous system. The primary autonomic
functions include cardiac regulation, control of respiration,
and vasomotor activity, which act largely unconsciously
. Exercise training has beneﬁcial roles in autonomic func-
tion, as indicated by improved heart rate recovery (HRR) and
heart rate variability (HRV) in various populations, such as
in sedentary individuals and chronic heart failure patients
. HRR refers to the declining rate of heart rate and is rec-
ognized as an indicator of cardiac prognosis . HRV is
deﬁned as consecutive heart beat variations in heart rate of
sinus rhythm. Reduced HRV represents attenuation of auto-
nomic regulation of sinoatrial node . Exercise works as
an intervention for autonomic dysfunction in type 2 diabetes
4 Oxidative Medicine and Cellular Longevity
by preserving HRV, HRR, and baroreﬂex sensitivity (BRS).
BRS is regulated by sympathetic and parasympathetic auto-
nomic nerves and is downregulated when there is cardiac
autonomic neuropathy .
Electrocardiogram is a noninvasive way to determine
cardiac conditions. Elevated R wave amplitudes and widened
QT intervals are reliable predictors of autonomic neuropa-
thy. Exercise training lowers heart rate and reduces QT inter-
val and R wave amplitudes on electrocardiogram in the
diabetic fatty rat model . In myocardial-infarcted rats,
structural remodeling leads to heterogeneity which causes
slow conduction and creates the generation of arrhythmias.
However, exercise training increases ratio of parasympathetic
over sympathetic tones and decreases probability of ventric-
ular arrhythmias of the MI rats . The mechanism of
exercise-induced improvement of arrhythmia might be
related to intrinsic electrophysiological cardioadaptive mech-
anisms because of decreased action potential duration
gradient between epicardial and endocardial cells in the
exercise-trained rats . The mechanisms by which exercise
improves autonomic function and preserves neurovascular
perfusion might be related to increasing NO bioavailability,
lowering angiotensin II (AngII) levels, and suppressing
chronic inﬂammation [87–90]. It is controversial that some
studies show that MI, stroke, ventricular tachycardia, or
ﬁbrillation can be elevated during the progress of physical
activity, so further studies about the duration, frequency,
and intensity need to be speciﬁcally investigated.
2.8. Antioxidant Defense. ROS of physiological levels are
responsible for signaling molecules to regulate normal
physical activities. On the contrary, excessively generated
ROS plays a crucial role in the initiation and progression
of CVD . ROS overproduction, decreased antioxidant
enzymes, and the downstream targets damage the subcel-
lular organelles, thus impairing the cardiovascular system.
Excessive ROS may decrease NO bioavailability and
NO/cGMP-dependent pathway which result in pathological
vasoconstriction and hypertension . ROS also initiates
inﬂammation with the activation of redox-sensitive tran-
scription factors and promotes expression of inﬂammatory
molecules . DNA is oxidized by ROS to form 8-oxo-dG
which can be detected in plasma and urine . AngII-
induced insulin resistance is relevant to ROS, which can
impair insulin signaling by decreasing phosphorylation of
IRS1 and Akt and translocation of GLUT4 to the plasma
Exercise attenuates oxidative damage in the blood vessel,
heart, brain, liver, skeletal muscle, and other organs. Exercise
reduces age-related mitochondrial oxidative damage and
increases mitochondrial NADH-cytochrome C reductase
activity in the heart of aged rats . By improving the antiox-
idant enzymes and redox status in many organs and patholo-
gies, the chronic treadmill exercise has an anti-inﬂammatory
eﬀect. Exercise alleviates oxidative stress through inactivating
ERK/AMPK signaling pathway and decreases expression of
inﬂammatory factors like IL-6, high-sensitivity CRP, TNFα,
and leucocyte diﬀerentiation antigens in diabetes . In
renovascular hypertensive rats, ROS released by vascular
endothelial cells impairs EDR by decreasing NO production
and facilitating vasoconstriction. Evidences indicate that
exercise reduces ROS, improves endothelial function, and
increases levels of elastin, ﬁbrillin, and NO. The elevated
cardiac MDA levels and MPO activity and depleted GSH
and catalase expression in hypertensive rats are totally
reversed by exercise training . BRS is improved by physi-
cal activity through reducing oxidative stress in the rostral
ventrolateral medulla to inhibit the sympathetic nerve
[98, 99]. In diabetic rats, the overproduction of ROS leads to
the abnormal aortic function and metabolic disorder.
Through exercise training, enzymes producing ROS such as
p67phox protein decrease and the enzymes taking part in
scavenging oxygen-free radicals, like superoxide dismutase
(SOD) 1, SOD2, catalase, and glutathione peroxidase (GPX),
are normalized, even increased [48, 100]. That means, all the
proteins taking part in oxidative stress tend to recover to
normal levels after exercise treatment .
Exercise upregulates the antioxidant defense mechanisms
through redox-sensitive transcription factors, NF-κB and
activator protein-1, and peroxisome proliferator-activated
receptor gamma coactivator 1-alpha (PGC-1α). Exercise nor-
malizes the aging-induced decline in mitochondrial oxidative
capacity through upregulating PGC-1α, redox-sensitive tran-
scription factors PPARγ, and the target antioxidant genes like
GPX and SOD2 [46, 102]. Through elevating laminar shear
stress, exercise upregulates SOD and downregulates NADPH
oxidase and VCAM-1. Through activating AMPK, exercise
training increases sirt3 and PPARγand the targets SOD1,
SOD2, GPX1, and catalase, thus resulting in less ROS produc-
tion and more ROS clearance in skeletal muscles .
Exercise increases thioredoxin reductase 1 and decreases
thioredoxin-interacting protein (TXNIP) in blood mononu-
clear cells and skeletal muscles, which promote antioxidant
ability and eliminate free radical [104, 105]. TXNIP is a regu-
lator of cellular redox signaling by binding thioredoxin to
inhibit the neutralization of ROS, indirectly enhancing the
oxidative stress . Nuclear factor erythroid 2-like factor
2 (Nrf2) is reported to be an important transcription factor
that performs antioxidant defense mechanisms through
Nrf2-ARE signaling to activate antioxidant gene expression
. Mounting evidences demonstrate that the Nrf2-ARE
signaling is downregulated in the aging heart, ischemia/reper-
fusion injury, and MI. Researchers ﬁnd that through chronic
exercise treatment, Nrf2 is upregulated and consequently
activates the key antioxidant enzyme expression such
as hemoxygenase-1, NADPH quinone oxidase-1, GPX1,
GPX2, glutathione reductase, γ-glutamyl cysteine ligase-
catalytic, γ-glutamyl cysteine ligase-modulatory, glucose-6-
phosphate dehydrogenase (G6PD), and catalase in the heart
[108, 109]. Based on these risk factors and studies, all major
cardiovascular societies recommend that a minimum of 5 days
a week of exercise, with at least 30 minutes of moderate-
intensity aerobic activity, is needed to prevent CVD .
3. The Recommendations for Physical Activity
Because of low-cost, low-risk, and nondrug intervention, the
European Society of Cardiology recommended that exercise
5Oxidative Medicine and Cellular Longevity
training should be provided by cardiac rehabilitation pro-
grams in patients with non-ST elevation acute coronary syn-
drome in 2015 . Physical activity is a part of everybody’s
life. However, the exercise intensity diﬀers between people
depending on the physical condition of individuals .
Although lots of studies show a positive correlation between
exercise and good health, a thorough physical evaluation is
necessary before an intensive exercise training program.
The intensity, mode, duration, and frequency of exercise
can strongly aﬀect outcome.
Aerobic exercise is deﬁned as using aerobic metabolism
to extract energy in muscles, mainly referring to low- to
moderate-intensity physical activities. As discussed above,
aerobic exercise has favorable eﬀects on lipid metabolism,
cardiac remodeling, post-MI heart failure, insulin resistance,
and endothelial function. Anaerobic exercise is an activity
that synthesize energy sources without using oxygen as
energy sources but glycolysis and fermentation. Anaerobic
exercise usually refers to high-intensity training, including
sprinting and power lifting. In several studies, high-
intensity exercise is recommended to lower TG and LDL.
Similar to aerobic exercise, anaerobic exercise also shows
positive inﬂuences on body mass index and blood pressure
. In some cases, high-intensity training shows more
beneﬁcial eﬀects on the cardiovascular system and EDR
compared to low-intensity training . The advantages
of high-intensity intermittent exercise refer to the fact that
the shorter time as 3-4 sessions/week will produce signiﬁcant
changes . However, there is a paradox of disadvantages
about anaerobic exercise training that the elevated mortality
and sudden death are brought by high-intensity activity. A
well-recognized viewpoint is that acute strenuous exercise
increases the risks for cardiovascular diseases, like MI, by
upregulating blood pressure . In conclusion, intensive
exercise should be intermittent especially for a long-term
program. Professional supervision and guidance are indis-
pensable when you conduct high-intensity exercise.
The general recommended exercise intensity for humans
from the American Heart Association to prevent CVD is 30
minutes, 5 times a week to reach at least 150 minutes per
week of moderate exercise, or 25 minutes, 3 times a week to
reach at least 75 minutes per week of vigorous activity. Indi-
viduals can choose one way of physical activity or combine
moderate and vigorous activities. They will also be beneﬁted
even if they divide the entire time into several parts of 10 to
15 minutes per day. For those who want to lower the risk
for heart attack and stroke, 40 minutes of moderate to vigor-
ous intensity aerobic activity, 3 or 4 times a week, is recom-
mended . Moderate-intensity exercise is more widely
performed among people who are interested in exercise and
enjoy rest time. Various studies show that the duration of
physical activity but not intensity is the primary factor lead-
ing to beneﬁts for humans .
Physical activity is regarded as an eﬃcient way to prevent
and counteract age-related changes in muscle and organic
function . As we know, any activity is better than none
and it is never too late to start for the elders . The
American College of Sports Medicine and the American
Heart Association recommend detailed description for elder
people that 30 minutes, 5 times a week, of moderate intensity,
or 20 minutes, 3 times a week, of vigorous intensity activity is
good for aging-related diseases. Strength training should
be included to enhance muscle groups and prevent falls
as 8-10 exercises with 10-15 repetitions, twice a week .
For the elders, joining exercise classes to improve balance
and prevent falls are strongly suggested . Exercise is
generally safe for older people unless for those elders
who already suﬀered from health problems doing resistance
Examples of aerobic exercise include cycling, dancing,
hiking, treadmill, climbing stairs, swimming, walking, and
any activities (the criterion is that you can talk without
breathing too hard). Anaerobic exercise refers to sprinting
and power lifting accompanied by accumulation of lactic acid
causing muscular fatigue . However, the deﬁnition of
moderate and vigorous exercise varies between individuals
because the indispensability to measure the level of intensity
bases on your ﬁtness and overall health.
4. Future Perspectives
Many people are robbed by the thinking all-or-nothing when
doing exercise. However, the low-level intensity training pro-
gram could beneﬁt you as long as you begin to change. Even
the easiest activity is better than nothing and whenever you
start is not too late .
There are also some limits for the exercise training when
applied to real patients’treatment. The existing studies do
not provide an exact guidance on the diverse intensity, dura-
tion, and frequency of exercise that may be suitable for the
diﬀerent kinds of diseases. In the future, personalization of
exercise will be an irresistible trend. For those young and in
healthy condition, it may be optional to consult a doctor
before they start an exercise program. However, personalized
exercise enables you to perform more speciﬁcally based on
your present ﬁtness level, interest, age, and gender .
For those old who have been inactive for a long period, it is
necessary to consult physicians who will measure some
indexes, like cardiorespiratory endurance, muscular strength,
muscular endurance, and ﬂexibility, and make graded exer-
cise tests for individuals . Also, for someone who has a
baseline disease, the extreme exercise training seems to trig-
ger the progression of disease. So tailored exercise would
bring beneﬁts not only for healthy humans but also for the
patients with chronic disease . For slow disease-related
declines of muscle strength, tailored exercise may focus on
the training to improve muscle strength and reduce the risk
of falls. For those who has type 2 diabetes, body weight con-
trol and enhancement of peripheral circulation are the ﬁrst
two goals to realize. For people with arthritis, tailored exer-
cise helps reduce joint stiﬀness and enhances muscle strength
[125, 128]. The systematical and overall exercise guidance
from a professional instructor is totally necessary. Personali-
zation of exercise training will be a huge demand and replace
the random mode of exercise today.
Although we get to know that exercise protects against
CVD through attenuating sympathetic activity, arterial pres-
sure, and heart rate, increasing blood ﬂow and endothelial
6 Oxidative Medicine and Cellular Longevity
NO production, causing vessel dilation, decreasing inﬂam-
matory cytokine and reactive oxygen species formation, the
exact mechanisms leading to transcriptional factor changes
or transcriptional modiﬁcations are not studied. So future
studies may be applied to the mechanisms of protective
eﬀects of exercise on the heart and vessels.
Conflicts of Interest
The authors declare that there is no conﬂict of interests
regarding the publication of this paper.
This work was supported by the grant from the Postgraduate
Innovational Funding Project of Hebei Provincial Education
Oﬃce (Grant CXZZBS2018064) and the Youth Fund for
Humanities and Social Sciences Research Projects in Higher
Institutions of Hebei Province (Grant SQ181136).
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