Soluble epoxide hydrolase inhibitors improve angiogenic function of endothelial progenitor cells via ERK/p38-mediated miR-126 upregulation in myocardial infarction mice after exercise.
Gui Yajun,Chen Jingyuan,Hu Jiahui,Liao Caixiu,Ouyang Minzhi,Deng Limin,Yang Jingmin,Xu Danyan
Experimental cell research
It is well established that exercise could protect against myocardial infarction (MI). Previously, we found that epoxyeicosatrienoic acids (EETs) could be induced by exercise and has been found to protect against MI via promoting angiogenic function of endothelial progenitor cells (EPCs). However, the underling mechanism of EETs in promoting EPC functions is unclear. C57BL/6 mice were fed with a novel soluble epoxide hydrolase inhibitor (sEHi), TPPU, to increase EET levels, for 1 week before undergoing MI surgery. Mice were then subjected to exercise training for 4 weeks. Bone marrow-derived EPCs were isolated and cultured in vitro. Exercise upregulated miR-126 expression but downregulated the protein levels of its target gene, Spred1, in EPCs from MI mice. TPPU further enhanced the effects of exercise on EPCs. Spred1 overexpression abolished the protective effects of TPPU on EPC functions. Downregulation of miR-126 by antagomiR-126 impaired the inhibitor effects of TPPU on Spred1 mRNA and protein expression. Additionally, TPPU upregulated miR-126 is partially mediated through ERK/p38 MAPK pathway. This study showed that sEHi promoted miR-126 expression, which might be related to the beneficial effect of sEHi on EPC functions in MI mice under exercise conditions, by increasing ERK and p38 MAPK phosphorylation and inhibiting Spred1.
Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction.
Liang Qiaoqin,Cai Mengxin,Zhang Jiaqi,Song Wei,Zhu Wanyu,Xi Lei,Tian Zhenjun
International journal of molecular sciences
Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups ( = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with HO (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.
Exercise training induces eNOS coupling and restores relaxation in coronary arteries of heart failure rats.
Couto Gisele K,Paula Suliana M,Gomes-Santos Igor L,Negrão Carlos Eduardo,Rossoni Luciana V
American journal of physiology. Heart and circulatory physiology
Exercise training (ET) has emerged as a nonpharmacological therapy for cardiovascular diseases because of its helpful milieu for improving vascular function. The aim of the present study was to assess whether ET reverses the alterations in vascular reactivity observed in heart failure (HF)-related coronary arteries and to elucidate the molecular mechanisms involved in these adjustments. Male Wistar rats were subjected to either coronary artery ligation or sham operation. Four weeks after the surgery, rats were divided into two groups: untrained HF (UHF) and exercise-trained HF (THF). ET was conducted on a treadmill for 8 wk. An untrained SO group was included in the study as a normal control. ET restored the impaired acetylcholine (ACh)- and sodium nitroprusside-induced relaxation in coronary arteries to levels of the control. Oxidative stress and reduced nitric oxide (NO) production were observed in UHF, whereas ET restored both parameters to the levels of the control. Expression levels of endothelial NO synthase (eNOS) and soluble guanylyl cyclase subunits were increased in coronary arteries of UHF rats but reduced in THF rats. Tetrahydrobiopterin restored ACh-induced NO production in the UHF group, indicating that eNOS was uncoupled. ET increased the eNOS dimer-to-monomer ratio and expression of GTP cyclohydrolase 1, thus increasing NO bioavailability. Taken together, these findings demonstrate that ET reverses the dysfunction of the NO/soluble guanylyl cyclase pathway present in coronary arteries of HF rats. These effects of ET are associated with increased GTP cyclohydrolase 1 expression, restoration of NO bioavailability, and reduced oxidative stress through eNOS coupling. NEW & NOTEWORTHY The present study provides a molecular basis for the exercise-induced improvement in coronary arteries function in heart failure. Increasing the expression of GTP cyclohydrolase 1, the rate-limiting enzyme in the de novo biosynthesis of tetrahydrobiopterin, exercise training couples endothelial nitric oxide synthase, reduces oxidative stress, and increases nitric oxide bioavailability and sensitivity in coronary arteries of heart failure rats.
Optimizing Outcomes in Cardiac Rehabilitation: The Importance of Exercise Intensity.
Taylor Jenna L,Bonikowske Amanda R,Olson Thomas P
Frontiers in cardiovascular medicine
Exercise based cardiac rehabilitation (CR) is recognized internationally as a class 1 clinical practice recommendation for patients with select cardiovascular diseases and heart failure with reduced ejection fraction. Over the past decade, several meta-analyses have generated debate regarding the effectiveness of exercise-based CR for reducing all-cause and cardiovascular mortality. A common theme highlighted in these meta-analyses is the heterogeneity and/or lack of detail regarding exercise prescription methodology within CR programs. Currently there is no international consensus on exercise prescription for CR, and exercise intensity recommendations vary considerably between countries from light-moderate intensity to moderate intensity to moderate-vigorous intensity. As cardiorespiratory fitness [peak oxygen uptake (VOpeak)] is a strong predictor of mortality in patients with coronary heart disease and heart failure, exercise prescription that optimizes improvement in cardiorespiratory fitness and exercise capacity is a critical consideration for the efficacy of CR programming. This review will examine the evidence for prescribing higher-intensity aerobic exercise in CR, including the role of high-intensity interval training. This discussion will highlight the beneficial physiological adaptations to pulmonary, cardiac, vascular, and skeletal muscle systems associated with moderate-vigorous exercise training in patients with coronary heart disease and heart failure. Moreover, this review will propose how varying interval exercise protocols (such as short-duration or long-duration interval training) and exercise progression models may influence central and peripheral physiological adaptations. Importantly, a key focus of this review is to provide clinically-relevant recommendations and strategies to optimize prescription of exercise intensity while maximizing safety in patients attending CR programs.
Closing Gaps in Lifestyle Adherence for Secondary Prevention of Coronary Heart Disease.
Aggarwal Monica,Ornish Dean,Josephson Richard,Brown Todd M,Ostfeld Robert J,Gordon Neil,Madan Shivank,Allen Kathleen,Khetan Aditya,Mahmoud Ahmed,Freeman Andrew M,Aspry Karen
The American journal of cardiology
The secondary prevention (SP) of coronary heart disease (CHD) has become a major public health and economic burden worldwide. In the United States, the prevalence of CHD has risen to 18 million, the incidence of recurrent myocardial infarctions (MI) remains high, and related healthcare costs are projected to double by 2035. In the last decade, practice guidelines and performance measures for the SP of CHD have increasingly emphasized evidence-based lifestyle (LS) interventions, including healthy dietary patterns, regular exercise, smoking cessation, weight management, depression screening, and enrollment in cardiac rehabilitation. However, data show large gaps in adherence to healthy LS behaviors and low rates of enrollment in cardiac rehabilitation in patients with established CHD. These gaps may be related, since behavior change interventions have not been well integrated into traditional ambulatory care models in the United States. The chronic care model, an evidence-based practice framework that incorporates clinical decision support, self-management support, team-care delivery and other strategies for delivering chronic care is well suited for both chronic CHD management and prevention interventions, including those related to behavior change. This article reviews the evidence base for LS interventions for the SP of CHD, discusses current gaps in adherence, and presents strategies for closing these gaps via evidence-based and emerging interventions that are conceptually aligned with the elements of the chronic care model.
Exercise and Coronary Heart Disease.
Advances in experimental medicine and biology
Coronary artery disease (CAD) can be obstructive or nonobstructive. Patients with nonobstructive and stable angina pectoris are usually women. Nonobstructive CAD is caused by endothelial dysfunction at the microvascular level, such as cardiac syndrome X and coronary slow flow syndrome. Even if coronary anatomy is nonobstructive, the presence of myocardial ischemia is a major determinant for the exercise program. CAD is a chronic inflammatory disease, and the progression of the disease can lead to a rapid change in the functional capacity of CAD patients. Exercise training is a major component of cardiac rehabilitation and reduces cardiovascular mortality, morbidity, and rehospitalization as well as improves psychological stress and controls risk factors of CAD, such as diabetes mellitus, hypertension, and obesity. It is possible that the quality of life of patients with CAD can be improved by using appropriate exercise therapy. However, the exercise programs among CAD patients are highly underutilized. This chapter will summarize the research progress of exercise in the prevention and treatment of CAD as well as how to create safe exercise programs and the importance of exercise for patients with CAD. In addition, exercise training has fundamental beneficial effects on ischemic and nonischemic heart failure.
[Exercise and Sports in the Therapy of Chronic Diseases - Coronary Heart Disease].
Schmied Christian M
Exercise and Sports in the Therapy of Chronic Diseases - Coronary Heart Disease Abstract. Despite increasingly advanced diagnostic and therapeutic methods, coronary heart disease and myocardial infarction continue to be by far the leading cause of death worldwide. This makes it all the more important in this context to make full use of known but far from optimally used therapeutic measures. Adequate physical activity in everyday life and additional targeted training lead to an evidence-based improvement in quality of life, a reduction in morbidity and above all to a significant reduction in cardiac and overall mortality. However, an accurate risk assessment of the individual patient with consistent training recommendations and monitoring is crucial in medical training advice. Today's sports recommendations for coronary heart disease have become much more liberal than before and allow patients with a relatively low risk of sudden cardiac death to do virtually any kind of exercise. This progressive posture, according to optimal risk assessment, is important, as newer data also show a dose-dependent increase in the preventive effect in coronary heart disesase patients with an increase in the extent of weekly training.
The effects of exercise training on lipid metabolism and coronary heart disease.
Muscella Antonella,Stefàno Erika,Marsigliante Santo
American journal of physiology. Heart and circulatory physiology
Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TGs), phospholipids, and apolipoproteins (Apos). ApoA1 is the major structural protein of high-density lipoprotein (HDL), accounting for ~70% of HDL protein, and mediates many of the antiatherogenic functions of HDL. Conversely, ApoB is the predominant low-density lipoprotein (LDL) Apo and is an indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Thus, the ratio of ApoB to ApoA1 (ApoB/ApoA1) is used as a surrogate marker of the risk of CHD related to lipoproteins. Elevated or abnormal levels of lipids and/or lipoproteins in the blood are a significant CHD risk factor, and several studies support the idea that aerobic exercise decreases CHD risk by partially lowering serum TG and LDL-cholesterol (LDL-C) levels and increasing HDL-C levels. Exercise also exerts an effect on HDL-C maturation and composition and on reverse C transport from peripheral cells to the liver to favor its catabolism and excretion. This process prevents atherosclerosis, and several studies showed that exercise training increases heart lipid metabolism and protects against cardiovascular disease. In these and other ways, it more and more appears that regular exercise, nutrition, and strategies to modulate lipid profile should be viewed as an integrated whole. The purpose of this review is to assess the effects of endurance training on the nontraditional lipid biomarkers, including ApoB, ApoA1, and ApoB/ApoA1, in CHD risk.