Natali AJ, Beenfits Magnetic field strength, Muscle recovery M, Turner DL, Harrison SM, White E. Magnetic field strength social aspect of Cardilvascular activities also Cardoovascular a fun environment and ebnefits. J Sci Med Foods That Boost Metabolism. In contrast, exercise-induced adaptations to cardiomyocyte mitochondria dampen oxidative damage caused by ischemia-reperfusion, resulting in reduced cardiac injury and decreasing the risk of ischemia-related cardiac dysfunction or death — Haskell WL. Lin X, Zhang X, Guo J, Roberts CK, McKenzie S, Wu WC, et al. Physical activity reduces heart attack risk For people who have coronary heart disease, regular aerobic activity helps the heart work better.

Cardiovascular health benefits -

A recent investigation also showed that individuals who maintain very high levels of physical activity ~3 times recommended levels have higher odds of developing CAC, particularly in white males In contrast, other studies report greater plaque stability due to calcification in exercisers, thus indicating that with higher levels of physical activity, plaque quality may be favorably impacted to lower the risk of cardiovascular events, despite a higher incidence of plaques and normal CAC scores , Nevertheless, as with other effects of exercise, the shape of the dose-response curve remains obscure and it is not clear at what levels of intensity and duration the effects of exercise begin to taper and where they start to become detrimental.

It is also unknown how this threshold of transition from benefit to harm is affected by personal demographic features such as age, sex, ethnicity, and baseline CVD risk. Other remaining questions are: can initiation of regular exercise, later in life, reverse the consequences of lifestyle choices made during earlier years of life e.

Yet, perhaps the most important questions relate to the mechanisms by which exercise imparts it remarkable benefits to cardiovascular health.

Indeed exercise has pervasive effects on immune cells—natural killer cells, neutrophils, monocytes, regulatory T cells, as well as the balance of T-cell types are all affected by exercise and it promotes a healthy anti-inflammatory milieu Nevertheless, how exercise affects inflammation and immunity and how these changes could account for the salubrious effects of exercise on cardiovascular disease risk and mortality are important questions that require additional careful investigations.

Additional work is also required to assess how nutrition affects exercise capacity as well as the cardiovascular benefits of exercise and how exercise affects the gut and the microbiome , In this regard, it is important to clearly delineate the extent to which nutritional supplements such as β-alanine and carnosine, which enhance the buffering capacity of muscle affect exercise capacity as well as muscle growth and hypertrophy.

Such work is essential and important not only for a basic understanding of the mechanisms of exercise-induced protection, but also for developing more effective exercise regimens, testing the efficacy of combined treatments involving exercise and dietary supplements, and for devising appropriate pharmacological interventions for those who would not or cannot exercise.

Figure 1. Overview of major cardiovascular effects of exercise. Abbreviations: HR, heart rate; LV, left ventricle; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; VSM, vascular smooth muscle; BP, blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; VLDL, very low density lipoprotein; TG, triglycerides; EPC, endothelial progenitor cell.

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. This work was supported in part by grants from the National Institutes of Health GM, HL and the American Heart Association 16SDG The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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A Exercise improves oxygen delivery throughout the body through promotion of vasodilation and angiogenesis — B Exercise increases mitochondrial biogenesis in adipocytes , , , skeletal muscle myotubes , and cardiomyocytes 14 , , C Exercise causes a long-term anti-inflammatory effect which is inversely related to the increased inflammation typically seen in CVD and obesity Myokines released from skeletal muscle during physical exercise partially mediate these anti-inflammatory effects, and promote inter-tissue cross talk to mediate further cardiovascular benefits — Exercise induces adaptations in several cell types and tissues throughout the body.

Exercise increases mitochondrial biogenesis in adipocytes , , , skeletal muscle myocytes , and cardiomyocytes 14 , , , increasing aerobic respiration within these tissues.

Additionally, exercise improves oxygen delivery throughout the body through vasodilation and angiogenesis — , protecting against ischemia-reperfusion injury in the heart , Further, exercise causes a long-term anti-inflammatory effect which is inversely related to the increased inflammation typically seen in CVD and obesity Many of the benefits sustained by exercise are due to mitochondrial adaptations throughout the body.

For example, exercise improves long-term cardiorespiratory fitness VO 2 by increasing the mitochondrial content and desaturation of myoglobin in skeletal muscle tissue, improving the oxidative capacity of skeletal muscle , , The increase of oxygen uptake and utilization by skeletal muscle as indicated by arteriovenous oxygen difference; a-vO 2 in response to regular exercise is protective against a decrease in obesity-related a-vO2, resulting in individuals to require more blood to receive the same amount of oxygen Mitochondrial biogenesis is augmented in cardiomyocytes in response to exercise 14 , , , This is likely due to enhanced activation of AMP-activated protein kinase AMPK and subsequent increase mitochondrial PGC-1α expression , Exercise also increases the ability of mitochondria to oxidize fatty acids the predominant substrate utilized in healthy myocardium , thus increasing the capacity for ATP synthesis 14 , — These exercise-induced enhancements of mitochondrial function are important in preventing cardiovascular dysfunctions often caused by obesity.

Obesity is associated with defective mitochondrial biogenesis in the myocardium and reduced mitochondrial capacity for oxidative phosphorylation and ATP synthesis , In heart failure, fatty acid uptake, and utilization is decreased , likely causing the heart failure associated shift toward glucose metabolism in order to preserve cardiovascular function , , However, in advanced heart failure, diabetes, or obesity, myocardial insulin resistance may develop, impairing glucose uptake and accelerating cardiovascular dysfunction — Importantly, insulin sensitivity is improved in response to regular exercise which is vital in reducing the risk of obesity-related insulin resistance.

Insulin has also been indicated to directly regulate mitochondrial metabolism by promoting induction of OPA1, a GTPase that controls mitochondrial cristae integrity, energetics and mitochondrial DNA maintenance , , thus indicating another potential mechanism of exercise-induced improvements in cardiovascular health through mitochondrial function enhancement.

Reactive oxygen species ROS are physiological byproducts of aerobic mitochondrial metabolism and while necessary for initiating cellular repair or apoptosis, increased levels of ROS are associated with inflammation and several forms of CVD While exercise increases the direct production of ROS by mitochondria, the net cellular ROS load is reduced by exercise due to increased action of antioxidant systems By increasing the ability of mitochondria to prevent oxidative damage, exercise-induced modifications to mitochondria protect against ischemia-reperfusion damage to the heart.

During ischemia, the absence of oxygen from the heart creates an environment in which the return of oxygenated blood flow leads to the induction of inflammation and oxidative stress rather than restoration of normal function In contrast, exercise-induced adaptations to cardiomyocyte mitochondria dampen oxidative damage caused by ischemia-reperfusion, resulting in reduced cardiac injury and decreasing the risk of ischemia-related cardiac dysfunction or death — Exercise training induces vascular adaptations to several tissues , In the heart, the increase in vascularization protects against vascular stress and reduces the likelihood of a cardiac event 24 — These adaptations are mediated through increased expression of vascular endothelial nitric oxide synthase eNOS.

Exercise increases the intensity of physiological shear stress, inducing the shear stress-dependent activity of c-Src in endothelial cells and increasing expression of eNOS 27 , In the vascular endothelium, eNOS catalyzes the production of nitric oxide NO which causes vasodilation, inhibits platelet aggregation and prevents leukocyte adhesion to vessel walls, thus reducing the onset of atherosclerosis, thrombosis, ischemia, or other cardiac events , Exercise also induces angiogenesis, however the mechanisms regulating this process are unclear.

It has been hypothesized that the increase in nitric oxide NO production after exercise upregulates pro-angiogenic factors, particularly vascular endothelial growth factor VEGF One recent study determined that male rats who underwent exercise training for 10 weeks after MI had increased Akt phosphorylation of eNOS, and reactivation of cardiac VEGF pathway activity, resulting in increased angiogenesis While the mechanisms are not completely defined, it is clear that exercise induces arteriogenesis, increases angiogenesis and protects against vascular stress, thus decreasing the possibility of a cardiac event — , , Inflammation is a complex yet normal biological reaction to damaging stimuli Chronic inflammation is associated with multiple diseases including obesity, T2D, and CVD , Excess consumption of nutrients causes cells including adipocytes , hepatocytes , islet cells , and skeletal muscle cells to activate the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB and activator protein 1 AP-1 , increase expression of toll-like receptor 4 TLR4 , , and stimulate the release of cytokines such as TNF-α, IL-6, IL-1β, and CCL2 , Exercise, however, results in a long-term anti-inflammatory effect , The exercise-induced reduction of meta-inflammation during disease is hypothesized by some to be related to downregulation of NF-κB — , but exercise also decreases monocyte accumulation and suppresses the release of TNF-α and other pro-inflammatory adipokines, creating an anti-inflammatory effect — Excess immune activation caused by obesity is of particular concern for vascular health, as activation of TLR4 causes monocyte recruitment and conversion to foam cells, driving the progression of atherosclerosis 67 , Exercise prevents the development of atherosclerosis by reducing expression of TLRs on monocytes and macrophages, which subsequently decreases the availability of TLR4 ligands and inhibiting pro-inflammatory cytokine production , , Exercise also decreases pro-inflammatory N-terminal pro b-type natriuretic NT-proBNP and high-sensitivity C-reactive protein hsCRP within the heart, both of which are predictors of heart failure in atherosclerosis , Skeletal muscle can act as a secretory organ by stimulating the production, secretion, and expression of specific myokines after contraction — Myokines are chemical messengers that function in an autocrine, paracrine, or endocrine manner to influence crosstalk between different organs including skeletal muscle, liver, and adipose tissue — They are of great interest with regards to cardiovascular health because the well-known protective actions of exercise on cardiovascular function are at least partially mediated by increased secretion of myokines Figure 2 Some myokines that impact cardiovascular health include IL-6, myonectin, Fstl1, and NDNF Figure 2.

Exercise-induced myokines mediate organ cross-talk and improve cardiometabolic health. A The myokine IL-6 inhibits TNF-α , reducing inflammation and protecting against the formation of atherosclerosis ; stimulates GLP-1 secretion causing improved insulin secretion ; increases lipolysis and fatty acid oxidation in adipose tissue and increases glucose uptake through the AMPK signaling pathway , C Myonectin MyoN increases fatty acid uptake in adipocytes and hepatocytes , and promotes protects against ischemic injury in the heart, possibly through Akt activation IL-6 was introduced as the first myokine over a decade ago Circulating levels of IL-6 are increased in response an acute bout of aerobic exercise , and can act in an endocrine fashion to improve metabolic and cardiovascular health.

Exercise-induced elevated concentrations of IL-6 can stimulate glucagon-like peptide-1 GLP-1 secretion from intestinal L cells and pancreatic α cells, leading to improvements in insulin secretion and glycemia IL-6 also increases lipolysis and fatty acid oxidation in adipose tissue and can increase glucose uptake through stimulation of the AMP-activated protein kinase AMPK signaling pathway , With regard to cardiovascular function, IL-6 can reduce inflammation by inhibiting tumor necrosis factor-α TNF- α This results in a protective effect on cardiovascular health because TNF- α is involved in the formation of atherosclerosis, development of heart failure, and subsequent complications, including myocardial infarction MI More investigation is required to determine the direct effects of IL-6 action on cardiovascular health.

Myonectin or CTRP15 is abundantly expressed in skeletal muscle and is increased in response to chronic aerobic exercise Importantly, injection of myonectin into wild-type mice decreases circulating free fatty acids levels by increasing fatty acid uptake in adipocytes and hepatocytes Myonectin has also been identified to have protective effects on cardiovascular health; mice deficient in Myonectin had enhanced ischemic injury in response to MI while systemic delivery of myonectin attenuated ischemic injury Further work is needed to determine whether these benefits are observed in response to an increase in myonectin after exercise.

Fstl1, also referred to as TSC, is a secreted glycoprotein that belongs to the follistatin family of proteins and is upregulated in skeletal muscle in response to exercise , , Expression of Fstl1 is also increased in ischemic and hypertrophic hearts of mice and functions in a protective manner Systemic administration of Fstl1 in both mouse and swine models led to reduced apoptosis, inflammation and injury size following ischemia-reperfusion , In vitro , treatment of cultured cardiomyocytes with Fstl1 reduces apoptosis in response to hypoxia-reoxygenation by activating Akt and AMPK , One recent study demonstrated that Fstl1 stimulates early fibroblast activation, which is required for acute repair and protects the heart from rupture after ischemia-reperfusion While the exact role of an exercise-induced increase in Flst1 on cardiovascular function has not been defined, these data indicate that Fstl1 is increased in response to exercise, and an increase in circulating Fstl1 functions to repair cardiovascular damage and improve cardiovascular function NDNF is a glycosylated protein secreted from the endothelial cells of skeletal muscle This pro-angiogenic affect is an important component in the recovery from MI; intramuscular administration of NDNF using an adenoviral vector improved systolic function in a mouse model after MI Increased NDNF levels are also associated with reduced myocardial hypertrophy and apoptosis in post-MI hearts Another study showed that down-regulation of NDNF by siRNA impairs recovery from ischemia-reperfusion injury Additionally, increased levels of NDNF released from skeletal muscle in response to exercise enhance fatty acid oxidation through activation of AMPK These data demonstrate the importance of NDNF as an endogenous ischemia- and exercise inducible factor that can enhance revascularization and therefore have a cardiovascular protective effect.

The rate of obesity-related cardiovascular disease is rapidly increasing, and often associated with additional co-morbidities including type 2 diabetes 3 , 6 , 8. It is clear that exercise reduces cardiovascular risk factors, and this reduction in risk factors is independent of changes to body weight or incidence of type 2 diabetes 75 — 77 , 79 , , Exercise is also an important therapeutic treatment for patients who have cardiovascular diseases 14 , further demonstrating the protective and restorative properties of exercise.

In patients with CVD, exercise improved endothelium-dependent vasodilatation, increased ejection fraction and exercise tolerance, improved quality of life, and reduced CVD-related mortality 10 , 91 , 92 , , , — Exercise improves cardiovascular health by several mechanisms including increased mitochondrial biogenesis and fatty acid oxidation 14 , , , — dilation of blood vessels causing improved myocardial perfusion 9 — 11 , and reduction of inflammation providing protection against the development of atherosclerosis 67 , , Myokines released from skeletal muscle during exercise also mediate systemic and cardiovascular health benefits through an anti-inflammatory action, increased fatty acid oxidation, increased glucose uptake, and improved insulin secretion and sensitivity , , , , — Importantly, several myokines IL-6, Myonectin, Fstl1, and NDNF have also been shown to have cardiovascular protective effects in response to ischemia-reperfusion injury — , , While it is clear that exercise is important, the mechanistic pathways behind exercise-induced benefits on cardiovascular health are still being identified.

Further understanding of the molecular mechanisms through which exercise improves cardiovascular function will lead to the development of therapeutics which can act in conjunction with exercise programs, and for individuals whom are unable or unwilling to exercise to amplify the beneficial effects of exercise.

Future research will investigate the effects of cardiac specific proteins on cardiovascular health, expanding research into the areas of system cross-talk will help delineate how other tissues, skeletal muscle in particular, can mediate cardiovascular improvements via myokine release.

How these myokines affect cardiovascular function, including adaptations to mitochondrial activity, angiogenesis and inflammatory responses will provide insight into new mechanisms for the beneficial effects of exercise on cardiovascular function.

Accordingly, myokines may act as potential targets for heart disease prevention and therapies. Recent studies have investigated the use of gene therapies, including the use of adeno-associated virus, on cardiovascular function.

While these therapies have not been fully optimized with remaining issues in immunogenicity, efficacy and genotoxicity , their development provides excitement for the potential therapies focused on exercise-induced myokines that improve cardiovascular function as a treatment for patients who are unable, or perhaps unwilling, to exercise.

Together these data highlight the importance of exercise and exercise-related therapies to both prevents the development of cardiovascular disease and promotes recovery and improved health in patients with CVD. KP, KKB, and KIS outlined, drafted, and contributed to the writing of the manuscript.

All authors approved the final version of the manuscript. This work was supported by National Institutes of Health Grants RHL and 17CSA to KIS and KDK to KKB. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: part I: general concepts. Both aerobic and muscle-building exercises can lower blood pressure slightly in people with normal blood pressure.

During a workout, muscles churn out a protein called GLUT-4, which improves the body's ability to process glucose sugar for energy, in part by making cells more sensitive to insulin, the hormone that enables cells to absorb glucose.

That's why exercise helps prevent and treat type 2 diabetes. Type 2 diabetes — which is closely linked to excess weight — doesn't exist in primitive societies, where physical activity is a way of life, he adds.

Either type of exercise can lower your HbA1c by 0. HbA1c is an average measure of your blood sugar over the past three months; a normal level is less than 5. Although exercise is widely touted for helping people burn calories and shed pounds, the amount of weight loss from exercise usually isn't dramatic unless routine exercise is coupled with a healthy, balanced, calorie-restricted diet.

However, exercise does help reduce visceral fat — the type that accumulates around the liver and other organs and is strongly linked to a higher risk of heart disease.

Exercise has also been shown to modestly lower triglycerides the most common type of fat in the bloodstream and harmful LDL cholesterol. Regular exercise is believed to help dampen the body's "fight or flight" response, which plays a role in chronic stress and anxiety. Exercise may also release naturally occurring cannabis- like chemicals that may boost your sense of well-being.

In addition, Dr. Baggish and colleagues recently showed that a single, minute bout of moderate exercise releases a number of proteins into the bloodstream, including brain-derived neurotrophic factor BDNF. BDNF has direct effects on brain function, especially with respect to mood and thinking ability.

All of these effects may explain why regular aerobic exercise is as effective as any antidepressant medication, he says. And while the heart may reap the bulk of exercise's many benefits, it may be the effect on your brain that inspires you to start moving more.

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