+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effect of myostatin deletion on cardiac and microvascular function

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          The objective of this study is to test the hypothesis that increased muscle mass has positive effects on cardiovascular function. Specifically, we tested the hypothesis that increases in lean body mass caused by deletion of myostatin improves cardiac performance and vascular function. Echocardiography was used to quantify left ventricular function at baseline and after acute administration of propranolol and isoproterenol to assess β‐adrenergic reactivity. Additionally, resistance vessels in several beds were removed, cannulated, pressurized to 60 mmHg and reactivity to vasoactive stimuli was assessed. Hemodynamics were measured using in vivo radiotelemetry. Myostatin deletion results in increased fractional shortening at baseline. Additionally, arterioles in the coronary and muscular microcirculations are more sensitive to endothelial‐dependent dilation while nonmuscular beds or the aorta were unaffected. β‐adrenergic dilation was increased in both coronary and conduit arteries, suggesting a systemic effect of increased muscle mass on vascular function. Overall hemodynamics and physical characteristics (heart weight and size) remained unchanged. Myostatin deletion mimics in part the effects of exercise on cardiovascular function. It significantly increases lean muscle mass and results in muscle‐specific increases in endothelium‐dependent vasodilation. This suggests that increases in muscle mass may serve as a buffer against pathological states that specifically target cardiac function (heart failure), the β‐adrenergic system (age), and nitric oxide bio‐availability (atherosclerosis). Taken together, pharmacological inhibition of the myostatin pathway could prove an excellent mechanism by which the benefits of exercise can be conferred in patients that are unable to exercise.

          Related collections

          Most cited references 34

          • Record: found
          • Abstract: found
          • Article: not found

          Effect of exercise on coronary endothelial function in patients with coronary artery disease.

          Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.
            • Record: found
            • Abstract: found
            • Article: not found

            Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial.

             R. Ross,  D Dagnone,  P Jones (2000)
            The independent effects of diet- or exercise-induced weight loss on the reduction of obesity and related comorbid conditions are not known. The effects of exercise without weight loss on fat distribution and other risk factors are also unclear. To determine the effects of equivalent diet- or exercise-induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat skeletal muscle mass, and insulin sensitivity in obese men. Randomized, controlled trial. University research center. 52 obese men (mean body mass index [+/-SD], 31.3 +/- 2.0 kg/m2) with a mean waist circumference of 110.1 +/- 5.8 cm. Participants were randomly assigned to one of four study groups (diet-induced weight loss, exercise-induced weight loss, exercise without weight loss, and control) and were observed for 3 months. Change in total, subcutaneous, and visceral fat; skeletal muscle mass; cardiovascular fitness; glucose tolerance and insulin sensitivity. Body weight decreased by 7.5 kg (8%) in both weight loss groups and did not change in the exercise without weight loss and control groups. Compared with controls, cardiovascular fitness (peak oxygen uptake) in the exercise groups improved by approximately 16% (P 0.2). However, these values were significantly greater than those in the control and exercise without weight loss groups (P < 0.001). Weight loss induced by increased daily physical activity without caloric restriction substantially reduces obesity (particularly abdominal obesity) and insulin resistance in men. Exercise without weight loss reduces abdominal fat and prevents further weight gain.
              • Record: found
              • Abstract: found
              • Article: not found

              Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors.

              Previous meta-analyses of randomized controlled trials on the effects of chronic dynamic aerobic endurance training on blood pressure reported on resting blood pressure only. Our aim was to perform a comprehensive meta-analysis including resting and ambulatory blood pressure, blood pressure-regulating mechanisms, and concomitant cardiovascular risk factors. Inclusion criteria of studies were: random allocation to intervention and control; endurance training as the sole intervention; inclusion of healthy sedentary normotensive or hypertensive adults; intervention duration of > or =4 weeks; availability of systolic or diastolic blood pressure; and publication in a peer-reviewed journal up to December 2003. The meta-analysis involved 72 trials, 105 study groups, and 3936 participants. After weighting for the number of trained participants and using a random-effects model, training induced significant net reductions of resting and daytime ambulatory blood pressure of, respectively, 3.0/2.4 mm Hg (P<0.001) and 3.3/3.5 mm Hg (P<0.01). The reduction of resting blood pressure was more pronounced in the 30 hypertensive study groups (-6.9/-4.9) than in the others (-1.9/-1.6; P<0.001 for all). Systemic vascular resistance decreased by 7.1% (P<0.05), plasma norepinephrine by 29% (P<0.001), and plasma renin activity by 20% (P<0.05). Body weight decreased by 1.2 kg (P<0.001), waist circumference by 2.8 cm (P<0.001), percent body fat by 1.4% (P<0.001), and the homeostasis model assessment index of insulin resistance by 0.31 U (P<0.01); HDL cholesterol increased by 0.032 mmol/L(-1) (P<0.05). In conclusion, aerobic endurance training decreases blood pressure through a reduction of vascular resistance, in which the sympathetic nervous system and the renin-angiotensin system appear to be involved, and favorably affects concomitant cardiovascular risk factors.

                Author and article information

                Physiol Rep
                Physiol Rep
                Physiological Reports
                John Wiley and Sons Inc. (Hoboken )
                30 November 2017
                December 2017
                : 5
                : 23 ( doiID: 10.1002/phy2.2017.5.issue-23 )
                [ 1 ] Department of Pharmacology Department of Physiology Vascular Biology Center Augusta University Augusta Georgia
                Author notes
                [* ] Correspondence

                David W. Stepp, Vascular Biology Center, 1459 Laney Walker Blvd, Augusta, Georgia 30912.

                Tel: 706‐721‐1949

                Fax: 706‐721‐9799

                E‐mail: dstepp@ 123456augusta.edu

                © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 6, Tables: 3, Pages: 10, Words: 5971
                Funded by: NHLBI
                Award ID: R01 HL124773
                Cardiovascular Physiology
                Skeletal Muscle
                Exercise Metabolism
                Original Research
                Original Research
                Custom metadata
                December 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.8 mode:remove_FC converted:13.12.2017


                Comment on this article