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Article ; Online: 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.

Pedersen, Lauren N / Blanks, Anson M / Bohmke, Natalie J / Mihalick, Virginia L / Franco, R Lee

2023 Volume 123, Issue 5, Page(s) 975–988

Abstract: 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 ...

Abstract	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 VO 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.
MeSH term(s)	Humans ; Monocytes/metabolism ; Leukocytes, Mononuclear ; Macrophages/metabolism ; Exercise/physiology ; Cardiovascular Diseases ; Lipoproteins, LDL/pharmacology
Chemical Substances	Lipoproteins, LDL
Language	English
Publishing date	2023-01-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124793-1
ISSN	1439-6327 ; 1432-1025 ; 0301-5548 ; 1439-6319
ISSN (online)	1439-6327 ; 1432-1025
ISSN	0301-5548 ; 1439-6319
DOI	10.1007/s00421-022-05131-x
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Article: Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise

Blanks, Anson M. / Pedersen, Lauren N. / Bohmke, Natalie / Mihalick, Virginia L. / Franco, R. Lee

Life sciences. 2022 June 15, v. 299

2022

Abstract: 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 ... ...

Abstract	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. 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. 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. 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). 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.
Keywords	atherosclerosis ; exercise ; flow cytometry ; macrophages ; monocytes ; phosphorylation ; premenopause ; risk
Language	English
Dates of publication	2022-0615
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120557
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Article ; Online: Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise.

Blanks, Anson M / Pedersen, Lauren N / Bohmke, Natalie / Mihalick, Virginia L / Franco, R Lee

Life sciences

2022 Volume 299, Page(s) 120557

Abstract	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 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.
MeSH term(s)	Exercise ; Female ; Humans ; Macrophages/metabolism ; Male ; Monocytes/metabolism ; Receptors, CCR2/metabolism ; Sex Characteristics
Chemical Substances	CCR2 protein, human ; Receptors, CCR2
Language	English
Publishing date	2022-04-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120557
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Article ; Online: Cardiopulmonary exercise testing during the COVID-19 pandemic.

Mihalick, Virginia L / Canada, Justin M / Arena, Ross / Abbate, Antonio / Kirkman, Danielle L

Progress in cardiovascular diseases

2021 Volume 67, Page(s) 35–39

Abstract: The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has presented a global public health emergency. Although predominantly a pandemic of acute respiratory disease, corona virus infectious disease-19 (COVID-19) ...

Abstract	The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has presented a global public health emergency. Although predominantly a pandemic of acute respiratory disease, corona virus infectious disease-19 (COVID-19) results in multi-organ damage that impairs cardiopulmonary (CP) function and reduces cardiorespiratory fitness. Superimposed on the CP consequences of COVID-19 is a marked reduction in physical activity that exacerbates CP disease (CPD) risk. CP exercise testing (CPET) is routinely used in clinical practice to diagnose CPD and assess prognosis; assess cardiovascular safety for rehabilitation; and delineate the physiological contributors to exercise intolerance and exertional fatigue. As such, CPET plays an important role in clinical assessments of convalescent COVID-19 patients as well as research aimed at understanding the long-term health effects of SARS-CoV-2 infection. However, due to the ventilatory expired gas analysis involved with CPET, the procedure is considered an aerosol generating procedure. Therefore, extra precautions should be taken by health care providers and exercise physiologists performing these tests. This paper provides recommendations for CPET testing during the COVID-19 pandemic. These recommendations include indications for CPET; pre-screening assessments; precautions required for testing; and suggested decontamination protocols. These safety recommendations are aimed at preventing SARS-CoV-2 transmission during CPET.
MeSH term(s)	COVID-19/immunology ; Exercise Test/methods ; Exercise Test/standards ; Humans ; Practice Guidelines as Topic ; Sterilization/methods
Language	English
Publishing date	2021-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209312-1
ISSN	1873-1740 ; 1532-8643 ; 0033-0620
ISSN (online)	1873-1740 ; 1532-8643
ISSN	0033-0620
DOI	10.1016/j.pcad.2021.04.005
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Article ; Online: LPS differentially affects expression of CD14 and CCR2 in monocyte subsets of Post-STEMI patients with hyperglycemia.

Blanks, Anson M / Pedersen, Lauren N / Caslin, Heather L / Mihalick, Virginia L / Via, Jeremy / Canada, Justin M / Van Tassell, Benjamin / Carbone, Salvatore / Abbate, Antonio / Lee Franco, R

Diabetes research and clinical practice

2022 Volume 191, Page(s) 110077

Abstract: Aims: Following ST-segment elevation myocardial infarction (STEMI), recruitment and activation of monocytes [classical (CD14: Methods: Post-STEMI subjects were identified as normal random glucose (NG, <98 mg/dL, n = 13) or impaired random glucose (IG, ...

Abstract	Aims: Following ST-segment elevation myocardial infarction (STEMI), recruitment and activation of monocytes [classical (CD14 Methods: Post-STEMI subjects were identified as normal random glucose (NG, <98 mg/dL, n = 13) or impaired random glucose (IG, ≥98 mg/dL, n = 26) and monocytes were analyzed for non-activated and LPS-activated (1 µg/mL for 4 h) CCR2 and CD14 expression. Results: Non-activated intermediate monocytes from IG showed decreased CD14 expression when compared to NG, which was maintained following LPS-activation. The NG group showed a larger absolute reduction in classical CCR2 expression, leading to a significant difference between NG and IG following LPS-activation. Conclusion: Results suggest a heightened response to pro-inflammatory activation in IG following STEMI, which may impair or delay post-STEMI myocardial healing, and thus increase the incidence of chronic heart failure. NIH 1R34HL121402.
MeSH term(s)	Blood Glucose/metabolism ; Humans ; Hyperglycemia/metabolism ; Lipopolysaccharide Receptors/immunology ; Lipopolysaccharides/pharmacology ; Monocytes/metabolism ; Receptors, CCR/metabolism ; Receptors, CCR2/metabolism ; Receptors, IgG/metabolism ; ST Elevation Myocardial Infarction
Chemical Substances	Blood Glucose ; CCR2 protein, human ; CD14 protein, human ; Lipopolysaccharide Receptors ; Lipopolysaccharides ; Receptors, CCR ; Receptors, CCR2 ; Receptors, IgG
Language	English
Publishing date	2022-09-08
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2022.110077
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Article ; Online: Impact of physical activity on monocyte subset CCR2 expression and macrophage polarization following moderate intensity exercise.

Blanks, Anson M / Wagamon, Thomas T / Lafratta, Lindsay / Sisk, Mabel G / Senter, Morgan B / Pedersen, Lauren N / Bohmke, Natalie / Shah, Attiya / Mihalick, Virginia L / Franco, R Lee

Brain, behavior, & immunity - health

2019 Volume 2, Page(s) 100033

Abstract: Coronary artery disease (CAD) is an immune-mediated disease in which CCR2 attracts classical, intermediate, and non-classical monocytes to the arterial intima where they differentiate to macrophages. Balance between pro-inflammatory M1 and anti- ... ...

Abstract	Coronary artery disease (CAD) is an immune-mediated disease in which CCR2 attracts classical, intermediate, and non-classical monocytes to the arterial intima where they differentiate to macrophages. Balance between pro-inflammatory M1 and anti-inflammatory M2 macrophages contributes to CAD prevention. Moderate to vigorous intensity physical activity (MVPA) elicits an immune response and reduces the incidence of CAD, however, the impact of prior MVPA on monocyte subset CCR2 expression and macrophage polarization following acute exercise is unknown. Purpose: To determine the impact of physical activity status on monocyte subset CCR2 surface expression and macrophage polarization in response to an acute bout of moderate intensity cycle ergometry. Methods: 24 healthy women and men (12 high physically active [HIACT]: ≥1500 METmin/wk MVPA & 12 low physically active [LOACT]: <600 METmin/wk MVPA) underwent an acute moderate intensity (60% VO Results: Intermediate monocyte CCR2 decreased in response to exercise in the HIACT group (PRE: 11409.0 ± 1084.0 vs. POST: 9524.3 ± 1062.4; p = 0.034). Macrophage CD206 was lower in the LOACT compared to the HIACT group at 1H (HIACT: 67.2 ± 5.6 vs. LOACT: 50.1 ± 5.2%; p = 0.040). Macrophage CD206 at 1H was associated with both PRE (r = 0.446, p = 0.043) and POST (r = 0.464, p = 0.034) non-classical monocyte CCR2. Conclusion: These data suggest that regular moderate to vigorous physical activity positively impacts both monocytes and macrophages following acute moderate intensity exercise and that this impact may contribute to the prevention of coronary artery disease.
Language	English
Publishing date	2019-12-27
Publishing country	United States
Document type	Journal Article
ISSN	2666-3546
ISSN (online)	2666-3546
DOI	10.1016/j.bbih.2019.100033
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Article ; Online: Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

Wohlford, George F / Van Tassell, Benjamin W / Billingsley, Hayley E / Kadariya, Dinesh / Canada, Justin M / Carbone, Salvatore / Mihalick, Virginia L / Bonaventura, Aldo / Vecchié, Alessandra / Chiabrando, Juan Guido / Bressi, Edoardo / Thomas, Georgia / Ho, Ai-Chen / Marawan, Amr A / Dell, Megan / Trankle, Cory R / Turlington, Jeremy / Markley, Roshanak / Abbate, Antonio

Journal of cardiovascular pharmacology

2020 Volume 77, Issue 1, Page(s) 49–60

Abstract: Abstract: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart ... ...

Abstract	Abstract: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.
MeSH term(s)	Administration, Oral ; Adult ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/adverse effects ; Anti-Inflammatory Agents/pharmacokinetics ; Double-Blind Method ; Exercise Tolerance/drug effects ; Female ; Heart Failure, Systolic/diagnosis ; Heart Failure, Systolic/drug therapy ; Heart Failure, Systolic/physiopathology ; Humans ; Male ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors ; Nitriles/administration & dosage ; Nitriles/adverse effects ; Nitriles/pharmacokinetics ; Recovery of Function ; Stroke Volume/drug effects ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects ; Virginia
Chemical Substances	Anti-Inflammatory Agents ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human ; Nitriles ; dapansutrile (2Z03364G96)
Language	English
Publishing date	2020-10-24
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/FJC.0000000000000931
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Article ; Online: 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.

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

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Article ; Online: Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise.

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Article ; Online: Cardiopulmonary exercise testing during the COVID-19 pandemic.

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Article ; Online: LPS differentially affects expression of CD14 and CCR2 in monocyte subsets of Post-STEMI patients with hyperglycemia.

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Article ; Online: Impact of physical activity on monocyte subset CCR2 expression and macrophage polarization following moderate intensity exercise.

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Article ; Online: Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

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