- Academic Editors
Normal-functioning endothelium is crucial to maintaining vascular homeostasis and inhibiting the development and progression of cardiovascular diseases such as atherosclerosis. Exercise training has been proven effective in regulating arterial endothelial function, and the effect of this regulation is closely related to exercise intensity and the status of arterial endothelial function. With this review, we investigated the effects of the exercise of different intensity on the function of arterial endothelium and the underlying molecular biological mechanisms. Existing studies indicate that low-intensity exercise improves arterial endothelial function in individuals who manifest endothelial dysfunction relative to those with normal endothelial function. Most moderate-intensity exercise promotes endothelial function in individuals with both normal and impaired arterial endothelial function. Continuous high-intensity exercise can lead to impaired endothelial function, and high-intensity interval exercise can enhance both normal and impaired endothelial function. In addition, it was demonstrated that the production of vasomotor factors, oxidative stress, and inflammatory response is involved in the regulation of arterial endothelial function under different-intensity exercise interventions. We posit that this synthesis will then provide a theoretical basis for choosing the appropriate exercise intensity and optimize the prescription of clinical exercise for persons with normal and impaired endothelium.
Arterial endothelial cells are located in the innermost layer of the vascular wall and are not only a physical barrier between the blood and the vascular wall but also an important regulator of vascular homeostasis. In addition to its regulation by chemical factors, arterial endothelial cells can respond adaptively to mechanical force signals such as fluid shear stress, circumferential stress, and stretch stress acting on the vessel wall. Then, in response, they can produce a variety of endogenous vasoactive factors such as nitric oxide (NO), prostacyclin, endothelin-1 (ET-1), and vascular cell adhesion molecule-1 (VACM-1), all of which are involved in the regulation of vascular tone, inflammatory response, oxidative stress, and other endothelial functions [1, 2, 3]. Studies have revealed that normal arterial endothelial function is essential for maintaining vascular health, while impaired endothelial function constitutes the initiating factor in the development and progression of cardiovascular diseases [4, 5]. Therefore, delaying or inhibiting cardiovascular diseases by augmenting arterial endothelial function has developed into a key strategy in the prevention and treatment of cardiovascular disease.
Exercise training is an effective method used to prevent and rehabilitate noninvasive cardiovascular diseases [6, 7, 8]. It is generally postulated that moderate-intensity exercise interventions improve arterial endothelial function by inducing an increase in the amplitude and frequency of blood shear stress, promoting endothelial nitric oxide synthase (eNOS) protein expression and NO release, and inhibiting the production of pro-inflammatory factors; whereas high-intensity exercise can lead to oxidative stress and decreased NO bioavailability, resulting in arterial endothelial dysfunction [9, 10, 11, 12, 13]. However, the actions of low-intensity exercise on endothelial function and the effects of different intensity exercise on normal and impaired individuals remain unknown. Therefore, in this paper we review the effects of low-, moderate-, and high-intensity exercise interventions on normal and impaired vascular endothelial functions and their governing molecular biological mechanisms, thus providing a theoretical basis for selecting the most appropriate exercise intensity for disparate populations.
Current indicators of endothelial function in arteries are divided into two main
categories: invasive indicator and non-invasive indicator. Endothelial function
was measured invasively in earlier studies using coronary angiography; this
modality allowed observation of the diastolic response of the vessel after
intracoronary injection of the endothelium-dependent vasodilator acetylcholine
(ACh). When endothelial function is normal, the addition of ACh induces diastole
of the coronary arteries as it stimulates the endothelial cells to secrete nitric
oxide. However, when endothelial dysfunction occurs, the coronary arteries are
not able to release NO effectively, and local vasoconstriction occurs due to
vascular contraction [14]. The principal non-invasive tests currently employed
are endothelium-dependent flow-mediated dilatation (FMD) and reactive
congestion-peripheral arterial tonometry (PAT). FMD is widely used in
cardiovascular clinical trials, and its application is based on high-resolution
ultrasonography to assess changes in brachial artery diameter in brachial artery
diameter in response to ischemia (typically 5 min). Normal blood vessels, in
response to various physiologic and chemical stimuli, usually dilate to modulate
blood flow and distribution. After reactive congestion is induced by cuff
compression, blood flow to the forearm generates blood shear stress that induces
endothelial cells to release NO, and this causes vascular dilatation. When
endothelial dysfunction occurs, NO release is reduced, resulting in an abnormal
diastolic response of the vascular wall to stimulation and attenuated FMD levels
[15, 16]. Maruhashi et al. [17] suggested that a value of FMD
In addition to the endothelial function tests described above, arterial endothelial function can also be evaluated by biochemical indicators. These include protein expression levels of the vasodilatory factor NO and vasoconstrictor factor ET-1; eNOS and its phosphorylation level [21]; the oxidative stress products reactive oxygen species (ROS) [12]; the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) [22]; and the inflammatory factors C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and von Willebrand factor (vWF) [11]. These biochemical indicators are usually used in experimental studies, and rarely served as clinical diagnostic parameters due to their invasive acquisition. At present, FMD is the gold standard for clinical diagnosis of endothelial dysfunction.
Exercise-induced changes in flow shear stress, vascular circumferential stress,
and stretch stress can modulate endothelial function, and the effect of this
modulation is related to the intensity of exercise. The selection of the
appropriate exercise intensity is therefore essential for the maintenance and
improvement of endothelial function. Exercise intensity is usually defined in
clinical and experimental studies in terms of the percentage of maximal oxygen
uptake (%VO
In addition, according to different exercise frequencies, exercise with different intensity is further divided into acute and long-term exercise. Acute exercise refers to a single bout of exercise, and long-term exercise is repetitive bouts of regular exercise. It is worth noting that acute high-intensity exercise includes acute high-intensity continuous exercise and acute high-intensity interval training (HIIT) or high-intensity interval exercise (HIIE). HIIT/HIIE is a form of intermittent exercise that has emerged in recent years, and encompasses the completion of numerous high-intensity exercise in a short period, and is interspersed with low-intensity exercise or rest between two high-intensity exercises [11]. Accordingly, long-term high-intensity exercise contains long-term high-intensity continuous exercise and long-term HIIT/HIIE.
To analyze the impact of different intensity exercise on persons with normal or impaired endothelial function to provide appropriate exercise intensity for them, the different populations were included in this review. These populations mainly include healthy young people, older adults, postmenopausal women, obese persons and patients with diabetes, hypertension or other cardiovascular diseases. Healthy young people tend to possess normal endothelial function, while impaired endothelial function is commonly associated with the other populations mentioned above. Some healthy elderly men also possess normal endothelial function. Accordingly, animals with normal and impaired endothelial function were included in the review [24, 25, 26]. It should be noted that human and animal experimental data on different intensity exercise regulating endothelial function were searched on PubMed, Web of Science and Google Scholar from 2003 to 2023. 70 pieces of literature were selected to review.
Extant studies have shown differential results in the modulation of arterial
endothelial function through low-intensity exercise (Table 1, Ref.
[9, 11, 13, 22, 27, 28]). Goto et al. [9] and Birk et al. [27] did
not uncover any significant changes in FMD levels or forearm blood flow in
response to ACh in healthy young adults for either acute exercise session or a
long-term low-intensity exercise intervention lasting 12 weeks; this indicated
that endothelial function did not undergo a significant improvement. However,
Shimizu et al. [11] found that RHI levels after 4 weeks of a
low-intensity resistance-exercise intervention in healthy elderly people were
elevated from 1.8
Research subjects | Exercise program | Changes in endothelial-function test indicators | Literature sources | ||||
Intensity | Duration and frequency of exercise | Forms | Indicators | Values (before vs. after exercsie) | Change | ||
Healthy young men (n = 10) | 25% VO |
30 min/d, 5–7 times/w, 12 w | Cycling | FBF | 5.0 |
NS | [9] |
Healthy young men (n = 10) | 50% HR |
One time, 30 min | Cycling | FMD | 6.3 |
NS | [27] |
Healthy elderly men (n = 20) | 20% 1RM | 15 min/d, 3 d/w, 4 w | Resistance exercise | RHI | 1.8 |
(↑) p |
[11] |
vWF | 175.7 |
(↓) p | |||||
Overweight and obese Postmenopausal women (n = 47) | 1 h/d, 2 d/w, 4 m | Walking | GPX | 9506 |
(↑) p |
[22] | |
saRHI | 1.97 |
(↑) p = 0.043 | |||||
Eight-week-old C57BL/6J mice (n = 6) | 5 m/min | 60 min/d, 6 d/w, 4 w | Treadmill training | The number of EPC | 497 |
(↑) p |
[28] |
db/db Sprague-Dawley rats (n = 11) | 10 m/min | 1 h/d, 6 w | Treadmill training | NO | 4.22 |
(↑) p |
[13] |
eNOS | 9.87 |
(↑) p | |||||
vWF | vWF decreased by 20.4% | (↓) p |
NS indicates no significant,
The results of experimental animal studies revealed that after 6 weeks of 10 m/min treadmill training in diabetic rats, serum NO levels and eNOS expression levels were elevated and vWF was decreased in the exercise group, proving beneficial to endothelial function; and appeared to prevent and improve diabetic cardiomyopathy [13]. Similarly, blood pressure was significantly reduced in rats suffering from severe hypertension after long-term low-intensity exercise training, and their impaired endothelium-dependent vasodilatory function and insulin sensitivity were also improved [29].
The reasons subserving the production of differential modulatory effects on arterial endothelial function with low-intensity exercise described in the aforementioned studies may have related to whether the human subjects or rats initially possessed healthy arterial endothelial function. As previously mentioned, healthy young people usually possess normal endothelial function, while impaired endothelial function tends to occur in healthy young people, older adults, postmenopausal women, obese persons and patients with cardiovascular diseases. However, whether the initial healthy or impaired endothelial function is a critical factor in different intensity exercise regulating endothelial function requires further study.
A series of studies have shown that acute and long-term moderate-intensity
exercise promote arterial endothelial function in healthy individuals as well as
in the elderly, hypertensives, diabetics, and patients after myocardial
infarction (Table 2, Ref. [9, 21, 28, 30, 31, 32, 33, 34, 35, 36, 37]). Boeno et al. [30]
ascertained that acute moderate-intensity resistance exercise accelerated
vasodilation by increasing nitrites and nitrates (NO
Research subjects | Exercise program | Changes in endothelial-function test indicators | Literature sources | ||||
Intensity | Duration and frequency of exercise | Form | Indicator | Values (before vs. after exercsie) | Change | ||
Sedentary middle-aged men (n = 11) | 50% 1RM | One time, 40 min | Resistance exercise | FMD | 12.5 |
(↑) p = 0.016 | [30] |
NO |
6.8 |
(↑) p = 0.007 | |||||
Healthy elderly (n = 11) | 70% VO |
60 min/d, 10 d | Treadmill walking or running | FMD | 10 |
(↑) p |
[32] |
Patients who underwent PCI after an acute heart attack (n = 20) | 50–60% HRR | One time, 30 min | Aerobic exercise | FMD | increased by 4.9% | (↑) p = 0.034 | [31] |
Patients with acute abdominal aortic aneurysm (n = 22) | 40% peak power ouput (PPO) | One time, 27 min | Aerobic exercise | FMD | 0.69% vs. 1.73% | (↑) p |
[36] |
Patients with type II diabetes mellitus (n = 13) | 65–85% HR |
1 h/d, 3 d/w, 12 w | Aerobic and resistance exercise | FMD | 7.62 |
(↑) p |
[34] |
Healthy young men (n = 8) | 50% VO |
30 min/d, 5–7 times/w, 12 w | Cycling | ACh | 13.1 |
(↑) p |
[9] |
Patients with hypertension (n = 42) | 60–80% HRR | 40–50 min/times, 3 times/w, 12 w | Treadmill running | FMD | 7.59 |
(↑) p = 0.02 | [33] |
NO |
9.4 |
(↑) p = 0.005 | |||||
CRP | 2.8 |
(↓) p = 0.03 | |||||
MCP-1 | 124.1 |
(↓) p = 0.009 | |||||
VCAM-1 | 1387.8 |
(↓) p = 0.03 | |||||
ET-1 | 6.4 |
(↓) p | |||||
Young men with hypertension (n = 18) | 40–50% HRR | One time, 40 min | Cycling | NO | 65–70.85 µmol/L | (↑) p |
[37] |
Five-week-old db/db mouse (n = 8) | 5.2 m/min | 1 h/d, 5 d/w, 7 w | Wheel training | Mn-SOD | (↑) p |
[21] | |
eNOS Ser1117 | |||||||
Three-month-old SHR (n = 8) | 18–20 m/min | 60 min/d, 5 d/w, 8 w | Treadmill training | ROS | (↑) p |
[35] | |
NO | (↓) p | ||||||
Eight-week-old C57BL/6J mice (n = 6) | 10 m/min | 60 min/d, 6 d/w, 4 w | Treadmill training | The number of EPC | 497 |
(↑) p |
[28] |
The effect of an exercise intervention on arterial endothelial function also
exerts a significant temporal effect, with the effect on endothelial function
diminishing or even disappearing after the end of the exercise. Naylor et
al. [34] found that 12 weeks of combined aerobic and resistance exercise in
adolescent type II diabetic patients produced a significant elevation in brachial
artery FMD levels from 7.62
The results of experimental animal studies showed that long-term
moderate-intensity wheel exercise was observed to normalize diabetes-related
endothelial dysfunction and improve insulin sensitivity in a diabetic mouse
model, and the results suggested a reversal of type II diabetic endothelial
dysfunction by enhancing NO bioavailability through elevated production of
mitochondrial manganese superoxide dismutase (Mn-SOD), total eNOS protein, and
phospho-eNOS (Ser1177) [21]. Furthermore, Ye et al. [35] trained
hypertensive rats to run at 18–20 m/min (55–65%
VO
In conclusion, most acute and long-term moderate-intensity exercise training effectively improve endothelial function in different populations, but their effects on endothelial function have certain time limitations. Therefore, both healthy individuals with normal endothelial function and those with endothelial dysfunction need to maintain an effective exercise regimen to improve endothelial function through long-term exercise. In addition, double or multiple unfavorable factors acting on endothelial function may be able to weaken or inhibit the improvement of moderate intensity exercise on endothelial function. Thus, people with endothelial dysfunction who expect to obtain a beneficial effect of exercise need to minimize the influence of adverse factors, such as reducing high sugar intake.
Some studies suggest that one bout or
repetitive bouts of sustained high-intensity exercises cause
oxidative stress and the development of cellular inflammatory responses, leading
to impaired endothelial function, while others suggest that repetitive bouts of
HIIT/HIIE exerts a positive effect on the regulation of arterial endothelial
function (Table 3, Ref. [9, 12, 27, 30, 35, 41, 42, 43, 44, 45, 46]). Birk et al. [27]
described a significant diminution in FMD levels from 6.6
Research subjects | Exercise program | Changes in endothelial-function test indicators | Literature sources | ||||
Intensity | Duration and frequency of exercise | Forms | Indicators | Values (before vs. after exercsie) | Change | ||
Healthy young men (n = 10) | 85% HR |
One time, 30 min | Cycling | FMD | 6.6 |
(↓) p |
[27] |
Young men (n = 9) | extreme sports | One time | Ironman triathlon | FMD | 8.7 vs. 3.2% | (↓) p |
[41] |
Sedentary middle-aged men (n = 11) | 80% 1RM | One time, 40 min | Resistance exercise | ET-1 | 20.02 |
(↓) p = 0.004 | [30] |
Healthy young men (n = 8) | 75% VO |
30 min/d, 5–7 times/w, 12 w | Cycling | 8-OHdG | 6.7 |
(↑) p |
[9] |
MDA-LDL | 69.0 |
(↑) p | |||||
Patients with hypertensive metabolic syndrome (n = 17) | 40% HRR 5 min, 60% HRR 5 min, 80% HRR5 min, recovery 40% HRR 5 min (HIIT) | 3 d/w, 8 w | Treadmill running | FMD | 6.5 |
(↑) p |
[43] |
NO |
38.5 |
(↑) p | |||||
Healthy elderly (n = 12) | 100% PPO, recovery 15 s, 2 × 20 min/time (HIIT) | 3 d/w, 6 w | Cycling | FMD | 4.8 |
(↑) p |
[42] |
Patients with type 1 diabetes (n = 12) | 60% HR |
40 min/d, 3 d/w, 8 w | Cycling | FMD | 5.7 |
(↑) p |
[46] |
C57BL/6 mice (n = 6) | Started at 5 m/min and increased by 4 m/min every 10 min until exhaution | One time | Treadmill training | NO | (↓) p |
[44] | |
Three-month-old SHR (n = 8) | 26–28 m/min | 60 min/d, 5 d/w, 8 w | Treadmill training | ROS | (↑) p |
[35] | |
NO | (↓) p | ||||||
Ten-week-old SHR rats (n = 24) | 80% VO |
1 h/d, 5 d/w, 6 w | Treadmill training | ROS | (↑) p |
[12] | |
NO | (↓) p | ||||||
Eight-week-old Zucker rats (n = 12) | 10 m/min (3 min) and 18 m/min (4 min) alternating 6 sets | 5 d/w, 10 w | Treadmill training | SOD | 5.82 |
(↑) p |
[45] |
GPx | 2.09 |
(↑) p |
Relevant experimental studies with animal models have shown that acute and long-term sustained high-intensity exercise leads to impaired endothelial function. Przyborowski et al. [44] ascertained that reduced NO production and elevated superoxide anion levels in mice after acute progressive-to-exhaustive exercise approached basal levels after 4 hours of recovery. Other investigators reported that long-term high-intensity continuous exercise increased oxidative stress levels in spontaneously hypertensive rats, leading to eNOS uncoupling, excess ROS production, and attenuated NO bioavailability - which, in turn, adversely affected endothelial function [12, 35]. In the study by Groussard et al. [45], SOD and GPx activities in Zucker obese rats rose after 10 weeks of HIIT exercise intervention, improving endothelial function by enhancing antioxidant-defense capabilities.
In summary, high-intensity exercise provokes specific changes to the regulation of arterial endothelial function. Acute or long-term high-intensity sustained exercises can cause inflammatory responses and oxidative stress, reduce NO bioavailability, and adversely affect endothelial function. Acute or long-term HIIT/HIIE, however, enhances arterial endothelial function; and, therefore, those individuals with insufficient exercise time can select HIIT/HIIE. However, because HIIT/HIIE requires several high-intensity exercises in a short period, strict control is needed in exercise intensity, exercise interval time, and exercise frequency to prevent the occurrence of adverse cardiovascular events.
As a vasodilator derived from endothelial cells, NO is catalyzed by activated eNOS to metabolize L-arginine. NO regulates vascular tone and also inhibits platelet aggregation and leukocyte adhesion, and is an important indicator of arterial endothelial function [47]. ET-1 is an active peptide secreted by endothelial cells and exerts a robust vasoconstrictive effect. Vascular endothelial dysfunction, then, is associated with a decrease in NO secretion as well as an increase in ET-1 secretion. Studies have shown that mechanical forces (including blood shear stress, circumferential stress, and stretch stress) are important physiologic regulators of the production of both NO and ET-1 in endothelial cells, with blood shear stress being the most important mechanical force stimulus regulating vascular endothelial function [3]. Acute and long-term moderate-intensity exercise and acute HIIE intervention augment perfusion, alter hemodynamic signaling, and induce the upregulation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway by increasing the frequency and amplitude of shear stress acting on the eNOS Ser1177 phosphorylation at the vascular wall. Furthermore, this activity activates and increases endogenous NO bioavailability and reduces ET-1 production, thereby improving vascular tone and arterial endothelial function [48, 49, 50, 51]. In contrast, acute high-intensity sustained exercise can uncouple eNOS, leading to a further drop in NO production as well as an elevation in ET-1 concentrations [30, 33]. In addition, acute HIIT exercise mediates increased levels of adipocytokine C1q/tumor necrosis factor-related protein 9 (CTRP9), which may benefit endothelial function in obese individuals by promoting eNOS phosphorylation [52].
Oxidative stress is a pathophysiologic state that results from an imbalance
between the oxidative and antioxidant systems and arises when redox homeostasis
within an organism is damaged. Dysregulation of redox homeostasis occurs when the
production of oxidants such as ROS (including superoxide anion, hydrogen
peroxide, and hydroxyl radical) exceeds the production of antioxidants such as
superoxide dismutase and glutathione, leading to impaired vascular endothelial
function [53]. Studies have shown that low levels of ROS are conducive to
maintaining normal cellular homeostasis and blood vessel function, while
overproduction of ROS leads to oxidative stress reactions that then lead to the
development and progression of cardiovascular diseases. Long-term
low-to-moderate-intensity exercise increases the expression of the body’s
antioxidant enzymes SOD and GPX, improves antioxidant enzyme defense systems,
maintains vascular homeostasis, and reduces the risk of cardiovascular disease by
augmenting antioxidant capacity as well as by reducing the overexpression of
oxidative enzymes (e.g., reduced nicotinamide adenine dinucleotide
phosphate-reduced oxidase and xanthine oxidase [35, 54]). In addition,
researchers have identified a mitochondrial inner membrane
uncoupling protein 2 (UCP2) that is an important negative regulator of ROS
production. Furthermore, they have found that the long-term moderate-intensity
exercise intervention upregulated UCP2 expression via the
peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1
Inflammatory responses can induce arterial endothelial dysfunction that
constitutes an important trigger for atherosclerosis and structural changes in
arteries. The exercise intervention effectively suppresses the inflammatory
response, and long-term low-to-moderate-intensity exercise reduces the expression
of pro-inflammatory proteins, such as CRP, MCP-1, tumor necrosis factor-alpha (TNF-
EPCs can differentiate into endothelial cells that are involved in mediating the repair of endogenous vascular endothelial injury and that play a key role in maintaining the structural and functional integrity of the vascular endothelium [61]. Long-term Exercise can increase the number of EPCs, increase the activity of eNOS, enhance the bioavailability of NO, regulate endothelial repair in angiogenesis, and prevent endothelial dysfunction by targeting EPCs [62]. Acute and long-term moderate-intensity aerobic or resistance exercise affects the mobilization of EPCs by augmenting related pro-angiogenic factors such as vascular endothelial growth factor (VEGF),stromal cell-derived factor-1, hypoxia-inducible factor-1, and matrix metalloproteinase-9 to enhance endogenous endothelial repair, which, in turn, repairs and maintains the vascular cytoarchitecture [63, 64, 65].
The release of a range of bioactive molecules in exercise via extracellular
vesicles has been identified as a novel phenomenon in mediating intercellular
communication that promotes beneficial effects in many systems in vivo,
and the exercise intervention can induce the release of exosomes from a variety
of tissues and thereby improve endothelial function. Exosomes are nano-sized tiny
extracellular vesicles that contain proteins, lipids, nucleotides, and other
biologically active substances; and these target endothelial cells through direct
lipid membrane fusion, receptor-ligand interactions, macropinocytosis,
endocytosis, and other pathways to regulate cellular behavior and mediate
biological effects. These actions then promote vascular neogenesis, the
regulation of vasoconstriction and diastole, and the inhibition of apoptosis and
other regulatory endothelial functions [66]. Exercise-induced exosome secretion
provides a novel and direct endogenous cardioprotective effect that is closely
related to the advancement of intercellular information exchange [67] by
exercise, the activation of the sprouty related EVH1 domain containing 1 (SPRED1)/VEGF signaling pathway [28], and increased
Ca
Exercise applied as a tool in noninvasive active health and cardiovascular disease rehabilitation can effectively modulate arterial endothelial function and thus prevent the onset and development of cardiovascular disease [71]. Through a systematic review of the regulation of different intensities of exercise on endothelial function in disparate populations, we ascertained that low-intensity exercise improved arterial endothelial function in individuals with impaired but not normal endothelial function, while most moderate-intensity exercise and HIIT enhanced endothelial function in both normal and impaired individuals. However, it is unclear as to which is better for those with impaired endothelial function, and systematic and comprehensive studies are, therefore, sorely needed. It is now generally accepted that high-intensity sustained exercise leads to oxidative stress and thus impaired endothelial function and that HIIT improves endothelial function. However, the safety of HIIT in individuals with cardiovascular disease requires further elucidation. Vasodilator production, oxidative stress, inflammatory response, angiogenesis, and exosome secretion have also been shown to be involved in the regulation of endothelial function at different exercise intensities (Fig. 1). Whether there are other potential mechanisms involving in the aforementioned responses necessitates further examination. In addition, we expect that in the near future, the beneficial effects of exercise can be replaced or partly replaced by modulating the abovementioned mechanisms or corresponding signal pathways, which is certainly heartening.
Potential mechanisms by which exercise of different intensity
modulates endothelial function in arteries. eNOS, endothelial nitric oxide synthase; NO, nitric oxide; GPX, glutathione peroxidase; SOD, superoxide dismutase; CRP, c-reactive protein; MCP-1, monocyte chemoattractant protein-1; TNF-
Ach, acetylcholine; CTRP9, c1q/tumor necrosis factor-related protein 9; CRP,
c-reactive protein; ET-1, endothelin-1; eNOS, endothelial nitric oxide synthase;
EPCs, endothelial progenitor cells; FMD, flow-mediated dilatation; GPX,
glutathione peroxidase; HIIT, high-intensity interval training; HR
MC and YXW had the idea for the paper, reviewed and edited it critically for important intellectual content. YXW and QQL performed the literature search. QQL, KRQ, WZ and XMG substantially contributed to the conception of the paper, wrote the manuscript, designed the figures and critically revised the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
Not applicable.
Not applicable.
This work was supported by the National Natural Science Foundation of China (Grant Nos. 32000927 and 31971243), Shandong Province Natural Science Foundation (Grant No. ZR2020QC092) and Domestic visiting program of Weifang Medical University.
The authors declare no conflict of interest.
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