Acute, but not chronic, aerobic exercise alters the impact of ex vivo LDL and fatty acid stimulation on monocytes and macrophages from healthy, young adults.

BACKGROUND: Elevated low-density lipoprotein (LDL) and triglyceride concentrations are associated with future cardiovascular risk in young adults. Conversely, chronic physical activity is generally accepted to reduce CVD risk. Atherosclerosis is a major underlying cause of CVD, and atherogenesis is mediated by peripheral monocytes and monocyte-derived macrophages. The study aimed to determine if an individual's physical activity level impacts the phenotype of monocytes and monocyte-derived macrophages when stimulated with LDL and fatty acid ex vivo. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy, young adults of differing physical activity levels before and after a single bout of moderate intensity exercise (25 min at 60% of VO2peak). PBMCs were stimulated with LDL and palmitate ex vivo prior to differentiation into macrophages. Monocyte subset percentages and monocyte-derived macrophage expression of phenotypic (CD86, CD206) and functional (CCR2, ERK 1/2) markers were evaluated by flow cytometry. RESULTS: Compared to baseline, ex vivo LDL and palmitate stimulation decreased (p = 0.038) non-classical monocyte percentage from 24.7 ± 3.2 to 21.5 ± 2.6% in all participants. When ex vivo lipid stimulation was preceded by acute exercise, non-classical monocyte percentage was similar to baseline levels (p = 0.670, 25.8 ± 2.15%). Macrophage CD86/CD206 was increased from 1.30 ± 0.14 to 1.68 ± 0.19 when preceded by acute exercise in all participants. No differences were observed between participants of differing physical activity levels. CONCLUSIONS: Findings suggest that acute exercise modulates monocyte phenotype after LDL and palmitate stimulation in a protective manner, however, chronic physical activity does not alter monocyte/macrophage responses to any experimental condition in this population.

Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise.

Monocyte chemokine receptor 2 (CCR2) and phosphorylated extra-cellular regulated kinase 1 & 2 (ERK1/2) impact macrophage differentiation and progression of atherosclerosis. Whereas aerobic exercise favorably modulates the immune system and reduces atherosclerotic risk, it is unknown whether sex differences exist in the monocyte/macrophage response to acute aerobic exercise. AIMS: To determine the impact of an acute bout of moderate intensity aerobic exercise on monocyte and macrophage CCR2 expression, ERK1/2 phosphorylation, and macrophage polarization in pre-menopausal women and men. MATERIALS AND METHODS: Blood samples were collected in 24 people (Women/Men; n = 12) prior to (PRE), immediately after a bout of moderate intensity cycle ergometry (POST), and 2 h (2H) following exercise. Monocyte and macrophage CCR2 and phosphorylated ERK1/2 as well as macrophage CD86 and CD206 were analyzed by flow cytometry. KEY FINDINGS: PRE classical monocyte CCR2 expression was greater in women compared to men (Women: 20546.2 ± 2306.4 vs. Men: 14437.6 ± 1201.9 AUF; p = 0.028) and was reduced in women at 2H (PRE: 20546.2 ± 2306.4 vs. 2H: 15856.9 ± 1314.4 AUF; p = 0.027). POST classical monocyte CCR2 expression was inversely associated (r = -0.697, p = 0.012) with POST classical monocyte ERK1/2 phosphorylation in women only. The percentage of CCR2+ macrophages was lower in women at POST (Women: 62.0 ± 8.9 vs. Men: 83.6 ± 3.1; p = 0.031) and at 2H (Women: 60.3 ± 8.4 vs. Men: 83.5 ± 3.0%; p = 0.016). SIGNIFICANCE: These data suggest that a single bout of moderate intensity aerobic exercise differentially impacts monocyte CCR2 expression and macrophage polarization in women compared to men.

Sarcopenic Obesity in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a public health epidemic that is projected to double over the next two decades. Despite the high prevalence of HFpEF, there are currently no FDA approved therapies for health-related outcomes in this clinical syndrome making it one the greatest unmet needs in cardiovascular medicine. Aging and obesity are hallmarks of HFpEF and therefore there is a high incidence of sarcopenic obesity (SO) associated with this syndrome. The presence of SO in HFpEF patients is noteworthy as it is associated with co-morbidities, worsened cardiovascular health, hospitalizations, quality of life, and mortality. Furthermore, SO plays a central role in exercise intolerance, the most commonly reported clinical symptom of this condition. The aim of this review is to provide insights into the current knowledge pertaining to the contributing pathophysiological mechanisms and clinical outcomes associated with HFpEF-related SO. Current and prospective therapies to address SO in HFpEF, including lifestyle and pharmaceutical approaches, are discussed. The urgent need for future research aimed at better understanding the multifaceted physiological contributions to SO in HFpEF and implementing interventional strategies to specifically target SO is highlighted.