Exercise Lowers Plasma Angiopoietin-Like 2 in Men with Post-Acute Coronary Syndrome

Abstract

Pro-inflammatory angiopoietin-like 2 (angptl2) promotes endothelial dysfunction in mice and circulating angptl2 is higher in patients with cardiovascular diseases. We previously reported that a single bout of physical exercise was able to reduce angptl2 levels in coronary patients. We hypothesized that chronic exercise would reduce angptl2 in patients with post-acute coronary syndrome (ACS) and endothelial dysfunction. Post-ACS patients (n = 40, 10 women) were enrolled in a 3-month exercise-based prevention program. Plasma angptl2, hs-CRP, and endothelial function assessed by scintigraphic forearm blood flow, were measured before and at the end of the study. Exercise increased VO2peak by 10% (p<0.05), but did not significantly affect endothelial function, in both men and women. In contrast, exercise reduced angptl2 levels only in men (-26±7%, p<0.05), but unexpectedly not in women (+30±16%), despite similar initial levels in both groups. Exercise reduced hs-CRP levels in men but not in women. In men, levels of angptl2, but not of hs-CRP, reached at the end of the training program were negatively correlated with VO2peak (r = -0.462, p = 0.012) and with endothelial function (r = -0.419, p = 0.033) measured at baseline: better initial cardiopulmonary fitness and endothelial function correlated with lower angptl2 levels after exercise. Pre-exercise angptl2 levels were lower if left ventricular ejection time was long (p<0.05) and the drop in angptl2 induced by exercise was greater if the cardiac output was high (p<0.05). In conclusion, in post-ACS men, angptl2 levels are sensitive to chronic exercise training. Low circulating angptl2 reached after training may reflect good endothelial and cardiopulmonary functions.

Serum Levels of Angiopoietin-Like Protein 2 and Obestatin in Iranian Women with Polycystic Ovary Syndrome and Normal Body Mass Index

“…Muramoto A and his colleagues stated that after a change in life style for a period of 3 months which continued for 6 months, a rapid decline was observed in ANGPTL2 levels in obese individuals that showed 2% or more weight loss [ 35 ]. Thorin-Trescases and colleagues reported in patients with acute coronary syndrome after 3 months of physical training, which the plasma levels of ANGPTL2 decreased to 26%, while body mass, lean and fat mass, waist circumference, and BMI were not affected by the exercise training program [ 36 ]. Also, in the study of Piche, M.E and colleagues found that after a bariatric surgery, a relative decrease (0% at 6 months, 18% at 1 year) in ANGPTL2 levels did not reflect a drastic decrease in weight (27% at 6 months, 37% at 1 year) and the two studies suggested that the decrease in ANGPTL2 levels after bariatric surgery or physical training is not a marker of adiposity [ 37 ], and it is stated that this factor also secreted by other cells such as the heart, kidneys, endothelial cells and macrophages [ 13 , 14 , 15 , 16 ].…”

The impact of high‐intensity interval training on ventricular remodeling in patients with a recent acute myocardial infarction—A randomized training intervention pilot study

“…Details on the inclusion and exclusion criteria have been previously described elsewhere. 17,18 Importantly, AMI (ST elevation myocardial infarction or non-ST elevation myocardial infarction) was based on the universal definition. 19 For more detailed information on the exclusion criteria see section S1 of the Supporting Information.…”

High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation

“…But it is not so clear-cut. We reported that in overweight patients with acute coronary syndrome, 3 months of physical training reduced significantly plasma ANGPTL2 levels independently of a weight loss: while ANGPTL2 levels were reduced by 26% in men with acute coronary syndrome, body mass, lean and fat mass, waist circumference, and BMI were not affected by the exercise training program [ 8 ]. On the other hand, we recently reported that in severely obese patients, the relatively low reduction of ANGPTL2 levels after bariatric surgery (0% at 6 months, 18% at 1 year) does not reflect the drastic weight reduction (27% at 6 months, 37% at 1 year), but rather improvement in diabetes, dyslipidemia, and inflammation [ 60 ].…”

“…In accordance with this hypothesis, we recently reported that in patients with severe chronic kidney disease, high ANGPTL2 circulating levels measured after kidney transplantation were associated with high serum endothelin-1 levels [ 48 ]. In addition, we showed that in patients with acute coronary syndrome, the reduction of ANGPTL2 levels induced by the training program correlated with endothelial function measured at baseline: better initial endothelial function correlated with lower ANGPTL2 levels reached after exercise [ 8 ]. Dysfunctional (mouse, human) and/or senescent (human) endothelial cells could therefore produce ANGPTL2, contributing to the proinflammatory environment.…”

“…High circulating levels of ANGPTL2 have indeed been proposed to be a biomarker for early diagnosis and recurrence of various types of cancers ( Table 2 ). Furthermore, increased levels of ANGPTL2 were reported in diabetes [ 5 , 44 – 47 ], chronic kidney disease [ 9 , 46 , 48 , 49 ], cardiovascular diseases [ 5 , 7 , 8 , 26 , 50 – 57 ], metabolic disorders including obesity [ 5 , 55 , 58 – 60 ], and other diseases (for review, [ 6 ]), including autoimmune diseases such as dermatomyositis [ 61 ] and rheumatoid arthritis [ 62 ] (Tables 1 and 3 ). ANGPTL2 levels in the circulation were also reported to be a predictor of major adverse cardiac events and death in diabetic [ 45 ] and renal transplant [ 48 ] patients.…”